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Monocyte Chemotactic Protein-1 (Cytokine, Receptors, and Gene Polymorphisms) in Hepatitis

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Biomarkers in Liver Disease

Abstract

In this review, we have described monocyte chemotactic protein-1 (MCP-1), its receptors, and polymorphisms of genes encoding MCP-1 and its receptors in relation to hepatitis of different etiologies. The MCP1 -2518 G allele is associated with upregulation of MCP-1 transcript, and subjects bearing the G allele produce more MCP-1 that is mainly involved in leukocyte recruitment and trafficking. The cell receptors that bind MCP-1 are CCR2 and CCR5. Polymorphisms of genes encoding receptor proteins may potentially alter MCP-1 affinity to receptors and decrease MCP-1 relevance.

Available results are suggestive that the G allele in MCP1 -2518 A/G is a risk allele for worse hepatitis C course and for higher severity of alcoholic hepatitis. CCR5 polymorphisms or mutations influence resolution of HCV/HBV infections and predict response to treatment of hepatitis C with interferon-alpha. Expression of MCP-1 in hepatic tissue specimens shows correlation with severity of liver disease and hepatic fibrosis. Direct correlations between serum MCP-1 concentration, hepatic expression of MCP1, and MCP1 -2518 G allele are usually not seen in hepatitis. Tested CCR2 polymorphisms were not predictive either for resolution of viral infections or hepatitis severity.

Larger randomized studies could be confirmative or not for establishment of many interesting results signalizing by MCP-1-associated data performed usually in groups showing too small sample power for definitive conclusions.

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Abbreviations

ALT:

Alanine aminotransferase

anti-HBs:

Antibodies to surface antigen of hepatitis B virus

anti-HCV:

Antibodies to hepatitis C virus

AST:

Aspartate aminotransferase

DARC:

Duffy antigen receptor for chemokines

DNA:

Deoxyribonucleic acid

GWAS:

Genome-wide association study

HBsAg:

Surface antigen of hepatitis B virus

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HD:

Hemodialysis

HLA:

Human leukocyte antigen

HWE:

Hardy–Weinberg equilibrium

IFN:

Interferon

IL:

Interleukin

LD:

Linkage disequilibrium

MAF:

Minor allele frequency

MCP1 :

Monocyte chemotactic protein-1 gene

MCP-1:

Monocyte chemotactic protein-1

MIP:

Macrophage inflammatory protein

mRNA:

Messenger ribonucleic acid

NK:

Natural killer

OMIM:

Online Mendelian Inheritance in Man

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

SNP:

Single nucleotide polymorphism

Th:

T helper

TNF:

Tumor necrosis factor

References

  • Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A. 1999;96:12766–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aguilar F, González-Escribano MF, Sánchez-Román J, Núñez-Roldán A. MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus. Tissue Antigens. 2001;58(5):335–8.

    Article  CAS  PubMed  Google Scholar 

  • Ahlenstiel G, Berg T, Woitas RP, Grünhage F, Iwan A, Hess L, Brackmann HH, Kupfer B, Schernick A, Sauerbruch T, Spengler U. Effects of the CCR5-Delta32 mutation on antiviral treatment in chronic hepatitis C. Hepatology. 2003;39:245–52.

    Article  CAS  Google Scholar 

  • Algood HM, Flynn JL. CCR5-deficient mice control Mycobacterium tuberculosis infection despite increased pulmonary lymphocytic infiltration. J Immunol. 2004;173:3287–96.

    Article  PubMed  Google Scholar 

  • Almarri A, Batchelor JR. HLA and hepatitis B infection. Lancet. 1994;344:1194–5.

    Article  CAS  PubMed  Google Scholar 

  • Andres PG, Beck PL, Mizoguchi E, Bhan AK, Dawson T, Kuziel WA, Maeda N, MacDermott RP, Podolsky DK, Reinecker HC. Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in an NK1.1 lymphocyte-associated Th2-type immune response in the intestine. J Immunol. 2000;164:6303–12.

    Article  CAS  PubMed  Google Scholar 

  • Ansel KM, Mc Heyzer-Willaims LJ, Ngo VN, McHeyzer-Williams MG, Cyster JG. In vivo activated CD4T cells upregulate CXC chemokine receptor 5 and reprogramme their response to lymphoid chemokines. J Exp Med. 1999;190:1123–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baeck C, Wehr A, Karlmark KR, Heymann F, Vucur M, Gassler N, Huss S, Klussmann S, Eulberg D, Luedde T, Trautwein C, Tacke F. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut. 2012;61:416–26.

    Article  CAS  PubMed  Google Scholar 

  • Baeck C, Wei X, Bartneck M, Fech V, Heymann F, Gassler N, Hittatiya K, Eulberg D, Luedde T, Trautwein C, Tacke F. Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C(+) macrophage infiltration in mice. Hepatology. 2014;59:1060–72.

    Article  CAS  PubMed  Google Scholar 

  • Barrett S, Ryan E, Crowe J. Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin. J Hepatol. 1999;30:979–83.

    Article  CAS  PubMed  Google Scholar 

  • Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.

    Article  CAS  PubMed  Google Scholar 

  • Ben-Selma W, Harizi H, Boukadida J. MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients. Mol Biol Rep. 2011;38:5413–9.

    Article  CAS  PubMed  Google Scholar 

  • Blease K, Mehrad B, Standiford TJ, Lukacs NW, Gosling J, Boring L, Charo IF, Kunkel SL, Hogaboam CM. Enhanced pulmonary allergic responses to Aspergillus in CCR2−/− mice. J Immunol. 2000;165:2603–11.

    Article  CAS  PubMed  Google Scholar 

  • Boring L, Gosling J, Chensue SW, Kunkel SL, Farese Jr RV, Broxmeyer HE, Charo IF. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest. 1997;100:2552–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buraczyńska M, Bednarek-Skublewska A, Buraczyńska K, Książek A. Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism as a potential risk factor for cardiovascular disease in hemodialyzed patients. Cytokine. 2008;44:361–5.

    Article  PubMed  CAS  Google Scholar 

  • Campbell EM, Charo IF, Kunkel SL, Strieter RM, Boring L, Gosling J, Lukacs NW. Monocyte chemoattractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2−/− mice: the role of mast cells. J Immunol. 1999;163:2160–7.

    CAS  PubMed  Google Scholar 

  • Chang HY, Ahn SH, Kim DY, Shin JS, Kim YS, Hong SP, Chung HJ, Kim SO, Yoo WD, Han KH. Association between CCR5 promoter polymorphisms and hepatitis B virus infection [Article in Korean]. Korean J Hepatol. 2005;11:116–24.

    CAS  PubMed  Google Scholar 

  • Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL. Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol. 1996;157:4602–8.

    CAS  PubMed  Google Scholar 

  • Cheong JY, Cho SW, Choi JY, Lee JA, Kim MH, Lee JE, Hahm KB, Kim JH. RANTES, MCP-1, CCR2, CCR5, CXCR1 and CXCR4 gene polymorphisms are not associated with the outcome of hepatitis B virus infection: results from a large scale single ethnic population. J Korean Med Sci. 2007;22:529–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Czaja MJ, Geerts A, Xu J, Schmiedeberg P, Ju Y. Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease. J Leuk Biol. 1994;55:120–6.

    CAS  Google Scholar 

  • Degré D, Lemmers A, Gustot T, Ouziel R, Trépo E, Demetter P, Verset L, Quertinmont E, Vercruysse V, Le Moine O, Devière J, Moreno C. Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates. Clin Exp Immunol. 2012;169:302–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Desmet V, Gerber M, Hoofnagle JH, Manns M, Scheuer P. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.

    Article  CAS  PubMed  Google Scholar 

  • Fanning LJ, Levis J, Kenny-Walsh E, Wynne F, Whelton M, Shanahan F. Viral clearance in hepatitis C (1b) infection: relationship with human leukocyte antigen class II in a homogeneous population. Hepatology. 2000;31:1334–7.

    Article  CAS  PubMed  Google Scholar 

  • Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003;23:47–58.

    Article  PubMed  Google Scholar 

  • Fenoglio C, Galimberti D, Lovati C, Guidi I, Gatti A, Fogliarino S, Tiriticco M, Mariani C, Forloni G, Pettenati C, Baron P, Conti G, Bresolin N, Scarpini E. MCP-1 in Alzheimer’s disease patients: a -2518G polymorphism and serum levels. Neurobiol Aging. 2004;25:1169–73.

    Article  CAS  PubMed  Google Scholar 

  • Fierro NA, Roman S, Realpe M, Hernandez-Nazara Z, Zepeda-Carrillo EA, Panduro A. Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients. Mem Inst Oswaldo Cruz. 2011;106:1007–13.

    Article  CAS  PubMed  Google Scholar 

  • Flex A, Gaetani E, Papaleo P, Straface G, Proia AS, Pecorini G, Tondi P, Pola P, Pola R. Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke. 2004;35:2270–5.

    Article  CAS  PubMed  Google Scholar 

  • Flores-Villanueva PO, Ruiz-Morales JA, Song CH, Flores LM, Jo EK, Montaño M, Barnes PF, Selman M, Granados J. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J Exp Med. 2005;202:1649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franci C, Wong LM, Van DJ, Proost P, Charo IF. Monocyte chemoattractant protein–3, but not monocyte chemoattractant protein–2, is a functional ligand of the human monocyte chemoattractant protein–1 receptor. J Immunol. 1995;154:6511–7.

    CAS  PubMed  Google Scholar 

  • Glas J, Török HP, Simperl C, König A, Martin K, Schmidt F, Schaefer M, Schiemann U, Folwaczny C. The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin. Clin Immunol. 2003;108:46–50.

    Article  CAS  PubMed  Google Scholar 

  • Glas J, Török HP, Tonenchi L, Schiemann U, Folwaczny C. The -2518 promoter polymorphism in the MCP-1 gene is not associated with liver cirrhosis in chronic hepatitis C virus infection. Gastroenterology. 2004;126:1930–1.

    Article  PubMed  Google Scholar 

  • Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC. The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J Exp Med. 1998;188:157–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goulding C, Murphy A, MacDonald G, Barrett S, Crowe J, Hegarty J, McKiernan S, Kelleher D. The CCR5-D32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source. Gut. 2005;54:1157–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grzegorzewska AE, Pajzderski D, Sowińska A, Jagodziński PP. Monocyte chemoattractant protein-1 gene (MCP-1-2518 A/G) polymorphism and serological markers of hepatitis B virus infection in hemodialysis patients. Med Sci Monit. 2014;20:1101–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu L, Rutledge B, Fiorillo J, Ernst C, Grewal I, Flavell R, Gladue R, Rollins B. In vivo properties of monocyte chemoattractant protein-1. J Leukoc Biol. 1997;62:577–80.

    CAS  PubMed  Google Scholar 

  • Gu B, Ye B, Mao WL, Ye JL. Monocyte chemotactic protein-1 as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C. Hepatogastroenterology. 2014;61:55–8.

    CAS  PubMed  Google Scholar 

  • Heesen M, Tanabe S, Berman MA, Yoshizawa I, Luo Y, Kim RJ, Post TW, Gerard C, Dorf ME. Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse transcriptase-polymerase chain reaction does not detect mRNA for the KC or new MCP-1 receptor. J Neurosci Res. 1996;45:382–91.

    Article  CAS  PubMed  Google Scholar 

  • Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, Satsangi J, Wright M, Zhang L, Thomas HC, Thursz M, Hill AV. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology. 2003;38:1468–76.

    Article  CAS  PubMed  Google Scholar 

  • Herfarth H, Göke M, Hellerbrand C, Mühlbauer M, Vogl D, Schölmerich J, Rogler G. Polymorphism of monocyte chemoattractant protein 1 in Crohn’s disease. Int J Colorectal Dis. 2003;18:401–5.

    Article  PubMed  Google Scholar 

  • Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.

    Article  CAS  PubMed  Google Scholar 

  • Karadeniz M, Erdogan M, Cetinkalp S, Berdeli A, Eroglu Z, Ozgen AG. Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy. Endocrine. 2010;37:513–7.

    Article  CAS  PubMed  Google Scholar 

  • Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F. Hepatic recruitment of the inflammatory Gr1 monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50:261–74.

    Article  CAS  PubMed  Google Scholar 

  • Karpus WJ, Kennedy KJ, Kunkel SL, Lukacs NW. Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines. J Exp Med. 1998;187:733–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kiani AN, Johnson K, Chen C, Diehl E, Hu H, Vasudevan G, Singh S, Magder LS, Knechtle SJ, Petri M. Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis. J Rheumatol. 2009;36:2224–30.

    Article  CAS  PubMed  Google Scholar 

  • Kim WR, Benson JT, Therneau TM, Torgerson HA, Yawn BP, Melton III LJ. Changing epidemiology of hepatitis B in a U.S. community. Hepatology. 2004;39:811–6.

    Article  PubMed  Google Scholar 

  • Kim MS, Day CJ, Morrison NA. MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. J Biol Chem. 2005;280:16163–9.

    Article  CAS  PubMed  Google Scholar 

  • Kim JK, Chon CY, Kim JH, Kim YJ, Cho JH, Bang SM, Ahn SH, Han KH, Moon YM. Changes in serum and ascitic monocyte chemotactic protein-1 (MCP-1) and IL-10 levels in cirrhotic patients with spontaneous bacterial peritonitis. J Interferon Cytokine Res. 2007;27:227–30.

    Article  CAS  PubMed  Google Scholar 

  • Kolattukudy PE, Niu J. Inflammation, endoplasmic reticulum stress, autophagy, and the monocyte chemoattractant protein-1/CCR2 pathway. Circ Res. 2012;110:174–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korenaga M, Wang T, Li Y, Showalter LA, Chan T, Sun J, Weinman SA. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem. 2005;280:37481–8.

    Article  CAS  PubMed  Google Scholar 

  • Ksiaa Cheikh Rouhou L, Gorgi YL, Skhiri HA, Aouadi H, Ayed SJ, Sfar I, Ayed K, Ben Abdallah T. Chemokine and chemokine receptor gene polymorphism in Tunisian hemodialysis patients with HCV infection. Arab J Nephrol Transplant. 2011;4:117–24.

    PubMed  Google Scholar 

  • Kurihara T, Warr G, Loy J, Bravo R. Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med. 1997;186:1757–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee B, Doranz BJ, Rana S, Yi Y, Mellado M, Frade JM, Martinez-A C, O’Brien SJ, Dean M, Collman RG, Doms RW. Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J Virol. 1998;72:7450–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leroy V, Vigan I, Mosnier JF, Dufeu-Duchesne T, Pernollet M, Zarski JP, Marche PN, Jouvin-Marche E. Phenotypic and functional characterization of intrahepatic T lymphocytes during chronic hepatitis C. Hepatology. 2003;38:829–41.

    Article  CAS  PubMed  Google Scholar 

  • Lettow I, Berres ML, Schmitz P, Müller T, Berg T, Neumann UP, Trautwein C, Wasmuth HE. A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection. Hum Immunol. 2011;72:273–7.

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection. Cell. 1996;86:367–77.

    Article  CAS  PubMed  Google Scholar 

  • Lu B, Rutledge BJ, Gu L, Fiorillo J, Lukacs NW, Kunkel SL, North R, Gerard C, Rollins BJ. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med. 1998;187:601–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lukacs NW, Chensue SW, Karpus WJ, Lincoln P, Keefer C, Strieter RM, Kunkel SL. C-C chemokines differentially alter interleukin-4 production from lymphocytes. Am J Pathol. 1997;150:1861–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol. 2001;2:102–7.

    Article  CAS  PubMed  Google Scholar 

  • Mandrekar P, Ambade A, Lim A, Szabo G, Catalano D. An essential role for MCP-1 in alcoholic liver injury: regulation of pro-inflammatory cytokines and hepatic steatosis. Hepatology. 2011;54:2185–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mantovani A, Bonecchi R, Locati M. Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol. 2006;6:907–18.

    Article  CAS  PubMed  Google Scholar 

  • Marra F, Tacke F. Roles for chemokines in liver disease. Gastroenterology. 2014;147:577–94e1.

    Article  CAS  PubMed  Google Scholar 

  • Marra F, DeFranco R, Grappone C, Milani S, Pastacaldi S, Pinzani M, Romanelli RG, Laffi G, Gentilini P. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration. Am J Pathol. 1998;152:423–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marra F, Romanelli RG, Giannini C, Failli P, Pastacaldi S, Arrighi MC, Pinzani M, Laffi G, Montalto P, Gentilini P. Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells. Hepatology. 1999;29:140–8.

    Article  CAS  PubMed  Google Scholar 

  • Mascheretti S, Hinrichsen H, Ross S, Buggisch P, Hampe J, Foelsch UR, Schreiber S. Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients. Clin Exp Immunol. 2004;136:328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsukawa A, Lukacs NW, Standiford TJ, Chensue SW, Kunkel SL. Adenoviral-mediated overexpression of monocyte chemoattractant protein-1 differentially alters the development of Th1 and Th2 type responses in vivo. J Immunol. 2000;164:1699–704.

    Article  CAS  PubMed  Google Scholar 

  • Matsuno K, Nomiyama H, Yoneyama H, Uwatoku R. Kupffer cell-mediated recruitment of dendritic cells to the liver crucial for a host defense. Dev Immunol. 2002;9:143–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDermott DH, Zimmerman PA, Guignard F, Kleeberger CA, Leitman SF, Murphy PM. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet. 1998;352:866–70.

    Article  CAS  PubMed  Google Scholar 

  • Meng ZF, Wang HJ, Yao X, Wang XY, Wen YM, Dai JX, Xie YH, Xu JQ. Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice. Chin Med J (Engl). 2012;125:3266–72.

    CAS  Google Scholar 

  • Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61:77–87.

    Article  PubMed  Google Scholar 

  • Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006;13:34–41.

    Article  CAS  PubMed  Google Scholar 

  • Morgan TR, Lambrecht RW, Bonkovsky HL, Chung RT, Naishadham D, Sterling RK, Fontana RJ, Lee WM, Ghany MG, Wright EC, O’Brien TR, Trial Group HALT-C. DNA polymorphisms and response to treatment in patients with chronic hepatitis C: results from the HALT-C trial. J Hepatol. 2008;49:548–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mostowska M, Lianeri M, Oko A, Mostowska A, Jagodziński PP. No association of monocyte chemoattractant protein-1 -2518 A/G polymorphism with the risk of primary glomerulonephritis in the Polish population. Mol Biol Rep. 2012;39:5933–41.

    Article  CAS  PubMed  Google Scholar 

  • Mühlbauer M, Bosserhoff AK, Hartmann A, Thasler WE, Weiss TS, Herfarth H, Lock G, Schölmerich J, Hellerbrand C. A novel MCP-1 gene polymorphism is associated with hepatic MCP-1 expression and severity of HCV-related liver disease. Gastroenterology. 2003;125:1085–93.

    Article  PubMed  Google Scholar 

  • Nahon P, Sutton A, Rufat P, Faisant C, Simon C, Barget N, Trinchet JC, Beaugrand M, Gattegno L, Charnaux N. Lack of association of some chemokine system polymorphisms with the risks of death and hepatocellular carcinoma occurrence in patients with alcoholic cirrhosis: a prospective study. Eur J Gastroenterol Hepatol. 2007;19:425–31.

    Article  CAS  PubMed  Google Scholar 

  • Nahon P, Sutton A, Rufat P, Simon C, Trinchet JC, Gattegno L, Beaugrand M, Charnaux N. Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis. World J Gastroenterol. 2008;14:713–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narumi S, Tominaga Y, Tamaru M, Shimai S, Okumura H, Nishioji K, Itoh Y, Okanoue T. Expression of IFN-inducible protein-10 in chronic hepatitis. J Immunol. 1997;158:5536–44.

    CAS  PubMed  Google Scholar 

  • Nischalke HD, Nattermann J, Fischer HP, Sauerbruch T, Spengler U, Dumoulin FL. Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C. Mediators Inflamm. 2004;13:357–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nomiyama H, Hieshima K, Nakayama T, Sakaguchi T, Fujisawa R, Tanase S, Nishiura H, Matsuno K, Takamori H, Tabira Y, Yamamoto T, Miura R, Yoshie O. Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes. Int Immunol. 2001;13:1021–9.

    Article  CAS  PubMed  Google Scholar 

  • Papayianni A, Alexopoulos E, Giamalis P, Gionanlis L, Belechri AM, Koukoudis P, Memmos D. Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events. Nephrol Dial Transplant. 2002;17:435–41.

    Article  CAS  PubMed  Google Scholar 

  • Park BL, Kim YJ, Cheong HS, Kim LH, Choi YH, Lee HS, Shin HD. Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance. Exp Mol Med. 2006;38:694–702.

    Article  CAS  PubMed  Google Scholar 

  • Peters W, Dupuis M, Charo IF. A mechanism for the impaired IFN-γ productioninC-C chemokine receptor 2 (CCR2) knockout mice: role of CCR2 in linking the innate and adaptive immune responses. J Immunol. 2000;165:7072–7.

    Article  CAS  PubMed  Google Scholar 

  • Peters W, Scott HM, Chambers HF, Flynn JL, Charo IF, Ernst JD. Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2001;98:7958–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–32.

    Article  CAS  PubMed  Google Scholar 

  • Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, Hergott D, Porter-Gill P, Mumy A, Kohaar I, Chen S, Brand N, Tarway M, Liu L, Sheikh F, Astemborski J, Bonkovsky HL, Edlin BR, Howell CD, Morgan TR, Thomas DL, Rehermann B, Donnelly RP, O’Brien TR. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 2013;45:164–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology. 2003;124:352–60.

    Article  CAS  PubMed  Google Scholar 

  • Rollins BJ. Monocyte chemoattractant protein 1: a potential regulator of monocyte recruitment in inflammatory disease. Mol Med Today. 1996;2:198–204.

    Article  CAS  PubMed  Google Scholar 

  • Rollins BJ, Walz A, Baggiolini M. Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. Blood. 1991;78:1112–6.

    CAS  PubMed  Google Scholar 

  • Rothenberg ME. Eotaxin: an essential mediator of eosinophil trafficking into mucosal tissues. Am J Respir Cell Mol Biol. 1999;21:291–5.

    Article  CAS  PubMed  Google Scholar 

  • Rovin BH, Lu L, Saxena R. A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun. 1999;259:344–8.

    Article  CAS  PubMed  Google Scholar 

  • Salama MK, Sabry D, Al-Ghussein MA, Ahmed R, AbdAllah S, Taha FM, Fathy W, Wadie MS, Nabih M, Abul-Fotouh A, Darwish T. Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients. World J Gastroenterol. 2014;20(33):11793–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sallusto F, Lenig D, Mackay CR, Lanzavecchia A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med. 1998;187:875–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382:722–5.

    Article  CAS  PubMed  Google Scholar 

  • Sarafi MN, Garcia-Zepeda EA, MacLean JA, Charo IF, Luster AD. Murine monocyte chemoattractant protein (MCP)–5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. J Exp Med. 1997;185:99–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarma NJ, Tiriveedhi V, Crippin JS, Chapman WC, Mohanakumar T. Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis. J Virol. 2014;88:3733–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sato N, Ahuja SK, Quinones M, Kostecki V, Reddick RL, Melby PC, Kuziel WA, Ahuja SS. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells: absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation. J Exp Med. 2000;192:205–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schnabel RB, Baumert J, Barbalic M, Dupuis J, Ellinor PT, Durda P, Dehghan A, Bis JC, Illig T, Morrison AC, Jenny NS, Keaney Jr JF, Gieger C, Tilley C, Yamamoto JF, Khuseyinova N, Heiss G, Doyle M, Blankenberg S, Herder C, Walston JD, Zhu Y, Vasan RS, Klopp N, Boerwinkle E, Larson MG, Psaty BM, Peters A, Ballantyne CM, Witteman JC, Hoogeveen RC, Benjamin EJ, Koenig W, Tracy RP. Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators. Blood. 2009;115:5289–99.

    Article  PubMed  CAS  Google Scholar 

  • Seki E, de Minicis S, Inokuchi S, Taura K, Miyai K, van Rooijen N, Schwabe RF, Brenner DA. CCR2 promotes hepatic fibrosis in mice. Hepatology. 2009;50:185–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shields PL, Morland CM, Salmon M, Qin S, Hubscher SG, Adams DH. Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C infected livers. J Immunol. 1999;163:6236–43.

    CAS  PubMed  Google Scholar 

  • Shen HY, Deng YC, Wang QM, Li QS, Xu Z. Expression of MCP-1 in the patients of chronic hepatitis B complicated with nonalcoholic fatty liver disease [Article in Chinese]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:975–8.

    CAS  PubMed  Google Scholar 

  • Simpson KJ, Henderson NC, Bone-Larson CL, Lukacs NW, Hogaboam CM, Kunkel SL. Chemokines in the pathogenesis of liver disease: so many players with poor defined roles. Clin Sci. 2003;104:47–63.

    Article  CAS  PubMed  Google Scholar 

  • Soo HM, Garzino-Demo A, Hong W, Tan YH, Tan YJ, Goh P, Lim SG, Lim SP. Expression of a full-length hepatitis C virus cDNA up-regulates the expression of CC chemokines MCP-1 and RANTES. Virology. 2002;303:253–7.

    Article  CAS  PubMed  Google Scholar 

  • Szalai C, Duba J, Prohászka Z, Kalina A, Szabó T, Nagy B, Horváth L, Császár A. Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients. Atherosclerosis. 2001a;158:233–9.

    Article  CAS  PubMed  Google Scholar 

  • Szalai C, Kozma GT, Nagy A, Bojszkó A, Krikovszky D, Szabó T, Falus A. Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J Allergy Clin Immunol. 2001b;108:375–81.

    Article  CAS  PubMed  Google Scholar 

  • Thio CL, Astemborski J, Bashirova A, Mosbruger T, Greer S, Witt MD, Goedert JJ, Hilgartner M, Majeske A, O’Brien SJ, Thomas DL, Carrington M. Genetic protection against hepatitis B virus conferred by CCR5Delta32: evidence that CCR5 contributes to viral persistence. J Virol. 2007;81:441–5.

    Article  CAS  PubMed  Google Scholar 

  • Thursz MR, Kwiatkowski D, Allsopp CE, Greenwood BM, Thomas HC, Hill AV. Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med. 1995;332:1065–9.

    Article  CAS  PubMed  Google Scholar 

  • Traynor TR, Huffnagle GB. Role of chemokines in fungal infection. Med Mycol. 2001;39:41–50.

    Article  CAS  PubMed  Google Scholar 

  • Traynor TR, Kuziel WA, Toews GB, Huffnagle GB. CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus neoformans infection. J Immunol. 2000;164:2021–7.

    Article  CAS  PubMed  Google Scholar 

  • Traynor TR, Herring AC, Dorf ME, Kuziel WA, Toews GB, Huffnagle GB. Differential roles of CC chemokine ligand/monocyte chemotactic protein-1 and CCR2 2 in the development of T1 immunity. J Immunol. 2002;168:4659–66.

    Article  CAS  PubMed  Google Scholar 

  • Uchida E, Anan F, Masaki T, Kaneda K, Nawata T, Eshima N, Saikawa T, Yoshimatsu H. Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis. Intern Med J. 2012;42:29–34.

    Article  CAS  PubMed  Google Scholar 

  • Vincent JL, Gustot T. Sepsis and cirrhosis: many similarities. Acta Gastroenterol Belg. 2010;73:472–8.

    CAS  PubMed  Google Scholar 

  • Wang WW, Ang SF, Kumar R, Heah C, Utama A, Tania NP, Li H, Tan SH, Poo D, Choo SP, Chow WC, Tan CK, Toh HC. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma. PLoS One. 2013;8:e68904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woitas RP, Ahlenstiel G, Iwan A, Rockstroh JK, Brackmann HH, Kupfer B, Matz B, Offergeld R, Sauerbruch T, Spengler U. Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. Gastroenterology. 2002;122:1721–8.

    Article  CAS  PubMed  Google Scholar 

  • Wu L, Paxton WA, Kassam N, Ruffing N, Rottman JB, Sullivan N, Choe H, Sodroski J, Newman W, Koup RA, Mackay CR. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med. 1997;185:1681–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu ZE, Xie YY, Chen JH, Xing LL, Zhang AH, Li BX, Zhu CM. Monocyte chemotactic protein-1 gene polymorphism and monocyte chemotactic protein-1 expression in Chongqing Han children with tuberculosis [in Chinese]. Zhonghua Er Ke Za Zhi. 2009;47:200–3.

    PubMed  Google Scholar 

  • Xue J, Chen F, Wang J, Wu S, Zheng M, Zhu H, Liu Y, He J, Chen Z. Emodin protects against concanavalin A-induced hepatitis in mice through inhibiting activation of the p38 MAPK-NF-kB signaling pathway. Cell Physiol Biochem. 2015;35:1557–70.

    Article  CAS  PubMed  Google Scholar 

  • Yang B, Houlberg K, Millward A, Demaine A. Polymorphisms of chemokine and chemokine receptor genes in Type 1 diabetes mellitus and its complications. Cytokine. 2004;26:114–21.

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Kurihara T, Ryseck RP, Yang Y, Ryan C, Loy J, Warr G, Bravo R. Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J Immunol. 1998;160:4018–25.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, 49 Przybyszewskiego Blvd., 60-355, Poznań, Poland

    Alicja E. Grzegorzewska

  2. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781 Poznań, 6 Święcickiego Str., 60-781, Poznań, Poland

    Adrianna Mostowska

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  1. Alicja E. Grzegorzewska
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  2. Adrianna Mostowska
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Correspondence to Alicja E. Grzegorzewska or Adrianna Mostowska .

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  1. Department of Biomedical Science, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

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Grzegorzewska, A.E., Mostowska, A. (2017). Monocyte Chemotactic Protein-1 (Cytokine, Receptors, and Gene Polymorphisms) in Hepatitis. In: Patel, V., Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7675-3_8

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