Prolactin in Inflammatory Response

  • Ana Laura Pereira Suarez
  • Gonzalo López-Rincón
  • Priscila A. Martínez Neri
  • Ciro Estrada-ChávezEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 846)


Prolactin (PRL) is a peptide hormone produced by the pituitary gland and diverse extrapituitary sites, which triggers activation of various signaling pathways after binding to its receptor (PRLr) resulting in the activation of specific genes associated with the pleiotropic activities of PLR. To date, various PRLr isoforms have been described, generated by post-transcriptional or post-translational processes. PRL has been associated with the modulation of a variety of actions in the immune response and inflammatory processes in several physiologic and pathologic conditions. However, PRL can have opposite effects, which might be regulated by interaction with the various isoforms of PRLR and PRL variants, as well as the cellular and molecular microenvironment influence.


Prolactin Prolactin receptor Inflammation Myeloid cells Cytokines 


  1. 1.
    Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317(5838):666–670. doi:10.1126/science.1142883PubMedGoogle Scholar
  2. 2.
    Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692. doi:10.1146/annurev.immunol.021908.132557PubMedGoogle Scholar
  3. 3.
    Baldocchi RA, Tan L, King DS, Nicoll CS (1993) Mass spectrometric analysis of the fragments produced by cleavage and reduction of rat prolactin: evidence that the cleaving enzyme is cathepsin D. Endocrinol 133(2):935–938. doi:10.1210/endo.133.2.8344226Google Scholar
  4. 4.
    Banks WA, Kastin AJ, Gutierrez EG (1994) Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci lett 179(1–2):53–56PubMedGoogle Scholar
  5. 5.
    Barton BA, Wedemeyer GA, Pankhurst NW, Kraak G, Van der Sumpter JP, McDonald G, Milligan L, Schreck CB, Potinger TD, Pickering AD, Balm PHM, Fletcher TC, Morgan JD (1997) Fish stress and health in aquaculture. Book Fish stress and health in aquaculture: 278Google Scholar
  6. 6.
    Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15(2):74–80. doi:10.1016/0167-5699(94)90137-6PubMedGoogle Scholar
  7. 7.
    Bellinger DL, Millar BA, Perez S, Carter J, Wood C, ThyagaRajan S, Molinaro C, Lubahn C, Lorton D (2008) Sympathetic modulation of immunity: relevance to disease. Cell Immunol 252(1–2):27–56. doi:10.1016/j.cellimm.2007.09.005PubMedCentralPubMedGoogle Scholar
  8. 8.
    Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW (1996) Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 17(6):639–669. doi:10.1210/edrv-17-6-639PubMedGoogle Scholar
  9. 9.
    Ben-Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29(1):1–41. doi:10.1210/er.2007-0017PubMedCentralPubMedGoogle Scholar
  10. 10.
    Berczi I, Quintanar-Stephano A, Kovacs K (2009) Neuroimmune regulation in immunocompetence, acute illness, and healing. Ann N Y Acad Sci 1153:220–239. doi:10.1111/j.1749-6632.2008.03975.xPubMedGoogle Scholar
  11. 11.
    Bernton EW, Meltzer MS, Holaday JW (1988) Suppression of macrophage activation and T-lymphocyte function in hypoprolactinemic mice. Science 239(4838):401–404PubMedGoogle Scholar
  12. 12.
    Besedovsky HO, del Rey A (1996) Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 17(1):64–102. doi:10.1210/edrv-17-1-64PubMedGoogle Scholar
  13. 13.
    Bignon C, Binart N, Ormandy C, Schuler LA, Kelly PA, Djiane J (1997) Long and short forms of the ovine prolactin receptor: cDNA cloning and genomic analysis reveal that the two forms arise by different alternative splicing mechanisms in ruminants and in rodents. J Mol Endocrinol 19(2):109–120PubMedGoogle Scholar
  14. 14.
    Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev19(3):225–268. doi:10.1210/edrv.19.3.0334PubMedGoogle Scholar
  15. 15.
    Bouckenooghe T, Sisino G, Aurientis S, Chinetti-Gbaguidi G, Kerr-Conte J, Staels B, Fontaine P, Storme L, Pattou F, Vambergue A (2014) Adipose tissue macrophages (ATM) of obese patients are releasing increased levels of prolactin during an inflammatory challenge: a role for prolactin in diabesity? Biochim Biophys Acta 1842(4):584–593. doi:10.1016/j.bbadis.2013.12.005PubMedGoogle Scholar
  16. 16.
    Boutin JM, Edery M, Shirota M, Jolicoeur C, Lesueur L, Ali S, Gould D, Djiane J, Kelly PA (1989) Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol Endocrinol 3(9):1455–1461. doi:10.1210/mend-3-9-1455PubMedGoogle Scholar
  17. 17.
    Brand JM, Frohn C, Cziupka K, Brockmann C, Kirchner H, Luhm J (2004) Prolactin triggers pro-inflammatory immune responses in peripheral immune cells. Eur Cytokine Netw 15(2):99–104PubMedGoogle Scholar
  18. 18.
    Branger J, van den Blink B, Weijer S, Madwed J, Bos CL, Gupta A, Yong CL, Polmar SH, Olszyna DP, Hack CE, van Deventer SJ, Peppelenbosch MP, van der Poll T (2002) Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia. J Immunol 168(8):4070–4077PubMedGoogle Scholar
  19. 19.
    Brooks CL (2012) Molecular mechanisms of prolactin and its receptor. Endocr Rev 33(4):504–525. doi:10.1210/er.2011-1040PubMedCentralPubMedGoogle Scholar
  20. 20.
    Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75(1):50–83. doi:10.1128/MMBR.00031-10PubMedCentralPubMedGoogle Scholar
  21. 21.
    Clapp C, Martial JA, Guzman RC, Rentier-Delure F, Weiner RI (1993) The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133(3):1292–1299. doi:10.1210/endo.133.3.7689950PubMedGoogle Scholar
  22. 22.
    Clapp C, Thebault S, Martinez de la Escalera G (2008) Role of prolactin and vasoinhibins in the regulation of vascular function in mammary gland. J Mammary Gland Biol Neoplasia 13(1):55–67. doi:10.1007/s10911-008-9067-7PubMedGoogle Scholar
  23. 23.
    Clevenger CV, Kline JB (2001) Prolactin receptor signal transduction. Lupus 10(10):706–718PubMedGoogle Scholar
  24. 24.
    Corbacho AM, Macotela Y, Nava G, Eiserich JP, Cross CE, Martinez de la Escalera G, Clapp C (2003) Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts. FEBS Lett 544(1–3):171–175PubMedGoogle Scholar
  25. 25.
    Corbacho AM, Valacchi G, Kubala L, Olano-Martin E, Schock BC, Kenny TP, Cross CE (2004) Tissue-specific gene expression of prolactin receptor in the acute-phase response induced by lipopolysaccharides. Am J Physiol Endocrinol Metab 287(4):E750–E757. doi:10.1152/ajpendo.00522.2003PubMedGoogle Scholar
  26. 26.
    Chavez-Rueda K, Legorreta-Haquet MV, Cervera-Castillo H, Sanchez L, Jara LJ, Zenteno E, Blanco-Favela F (2005) Prolactin effect on CD69 and CD154 expression by CD4+cells from systemic lupus erythematosus patients. Clin Exp Rheumatol 23(6):769–777PubMedGoogle Scholar
  27. 27.
    Chuang E, Molitch ME (2007) Prolactin and autoimmune diseases in humans. Acta Biomed 78(Suppl 1):255–261PubMedGoogle Scholar
  28. 28.
    Davis JA, Linzer DI (1989) Expression of multiple forms of the prolactin receptor in mouse liver. Mol Endocrinol 3(4):674–680. doi:10.1210/mend-3-4-674PubMedGoogle Scholar
  29. 29.
    De Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A (2005) Prolactin and autoimmunity. Pituitary 8(1):25–30. doi:10.1007/s11102-005-5082-5PubMedGoogle Scholar
  30. 30.
    Deckx N, Lee WP, Berneman ZN, Cools N (2013) Neuroendocrine immunoregulation in multiple sclerosis. Clin Dev Immunol 2013:705232. doi:10.1155/2013/705232PubMedCentralPubMedGoogle Scholar
  31. 31.
    Dogusan Z, Hooghe R, Verdood P, Hooghe-Peters EL (2001) Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes. J Neuroimmunol 120(1–2):58–66PubMedGoogle Scholar
  32. 32.
    Duenas Z, Rivera JC, Quiroz-Mercado H, Aranda J, Macotela Y, Montes de Oca P, Lopez-Barrera F, Nava G, Guerrero JL, Suarez A, De Regil M, Martinez de la Escalera G, Clapp C (2004) Prolactin in eyes of patients with retinopathy of prematurity: implications for vascular regression. Invest Ophthalmol Vis Sci 45(7):2049–2055PubMedGoogle Scholar
  33. 33.
    Edwards CK, 3rd, Ghiasuddin SM, Schepper JM, Yunger LM, Kelley KW (1988) A newly defined property of somatotropin: priming of macrophages for production of superoxide anion. Science 239(4841 Pt 1):769–771Google Scholar
  34. 34.
    Elsea CR, Roberts DA, Druker BJ, Wood LJ (2008) Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-fluorouracil, and doxorubicin without affecting tumoricidal activity. PloS ONE 3(6):e2355. doi:10.1371/journal.pone.0002355PubMedCentralPubMedGoogle Scholar
  35. 35.
    Featherstone K, White MR, Davis JR (2012) The prolactin gene: a paradigm of tissue-specific gene regulation with complex temporal transcription dynamics. J Neuroendocrinol 24(7):977–990. doi:10.1111/j.1365-2826.2012.02310.xPubMedCentralPubMedGoogle Scholar
  36. 36.
    Feola RP, Collins MT, Czuprynski CJ (1999) Hormonal modulation of phagocytosis and intracellular growth of Mycobacterium avium ss. paratuberculosis in bovine peripheral blood monocytes. Microb Pathog 26(1):1–11. doi:10.1006/mpat.1998.0246PubMedGoogle Scholar
  37. 37.
    Filipin Mdel V, Brazao V, Santello FH, Caetano LC, Toldo MP, do Prado JC Jr. (2011) Prolactin: does it exert an up-modulation of the immune response in Trypanosoma cruzi-infected rats? Vet Parasitol 181(2–4):139–145. doi:10.1016/j.vetpar.2011.04.008PubMedGoogle Scholar
  38. 38.
    Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, McGuire SR, List RP, Day DE, Hoesel LM, Gao H, Van Rooijen N, Huber-Lang MS, Neubig RR, Ward PA (2007) Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 449(7163):721–725. doi:10.1038/nature06185PubMedGoogle Scholar
  39. 39.
    Freeman ME, Kanyicska B, Lerant A, Nagy G (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80(4):1523–1631PubMedGoogle Scholar
  40. 40.
    Fu YK, Arkins S, Fuh G, Cunningham BC, Wells JA, Fong S, Cronin MJ, Dantzer R, Kelley KW (1992) Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. J Clin Invest 89(2):451–457. doi:10.1172/JCI115605PubMedCentralPubMedGoogle Scholar
  41. 41.
    Gala RR (1991) Prolactin and growth hormone in the regulation of the immune system. Proc Soc Exp Biol Med 198(1):513–527PubMedGoogle Scholar
  42. 42.
    Garcia C, Aranda J, Arnold E, Thebault S, Macotela Y, Lopez-Casillas F, Mendoza V, Quiroz-Mercado H, Hernandez-Montiel HL, Lin SH, de la EGM, Clapp C (2008) Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2. A-dependent eNOS inactivation. J Clin Invest 118(6):2291–2300. doi:10.1172/JCI34508PubMedCentralPubMedGoogle Scholar
  43. 43.
    Gerlo S, Verdood P, Hooghe-Peters EL, Kooijman R (2005) Modulation of prolactin expression in human T lymphocytes by cytokines. J Neuroimmunol 162(1–2):190–193. doi:10.1016/j.jneuroim.2005.02.008PubMedGoogle Scholar
  44. 44.
    Gillette DD, Tridandapani S, Butchar JP (2014) Monocyte/macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets? Front Cell Infect Microbiol 4:18. doi:10.3389/fcimb.2014.00018PubMedCentralPubMedGoogle Scholar
  45. 45.
    Goffin V, Kelly PA (2002) Growth-promoting actions of prolactin, the hormone of lactation. J Pediatr Endocrinol Metab 15(6):787–788PubMedGoogle Scholar
  46. 46.
    Goffin V, Ferrag F, Kelly P (1998) Molecular aspects of prolactin and growth hormone receptors. In: LeRoithD(ed) Advances in molecular and cellular endocrinology, Vol 2:1–33Google Scholar
  47. 47.
    Goffin V, Binart N, Touraine P, Kelly PA (2002) Prolactin: the new biology of an old hormone. Annu Rev Physiol 64:47–67. doi:10.1146/annurev.physiol.64.081501.131049PubMedGoogle Scholar
  48. 48.
    Gonzalez C, Corbacho AM, Eiserich JP, Garcia C, Lopez-Barrera F, Morales-Tlalpan V, Barajas-Espinosa A, Diaz-Munoz M, Rubio R, Lin SH, Martinez de la Escalera G, Clapp C (2004) 16 K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. Endocrinol 145(12):5714–5722. doi:10.1210/en.2004-0647Google Scholar
  49. 49.
    Gordon S (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111(7):927–930PubMedGoogle Scholar
  50. 50.
    Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32(5):593–604. doi:10.1016/j.immuni.2010.05.007PubMedGoogle Scholar
  51. 51.
    Harris J, Bird DJ (2000) Modulation of the fish immune system by hormones. Vet Immunol Immunopathol 77(3–4):163–176PubMedGoogle Scholar
  52. 52.
    Hooghe R, Dogusan Z, Martens N, Velkeniers B, Hooghe-Peters EL (2001) Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. Lupus 10(10):719–727PubMedGoogle Scholar
  53. 53.
    Hu ZZ, Meng J, Dufau ML (2001) Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. J Biol Chem 276(44):41086–41094. doi:10.1074/jbc.M102109200PubMedGoogle Scholar
  54. 54.
    Jara LJ, Lavalle C, Fraga A, Gomez-Sanchez C, Silveira LH, Martinez-Osuna P, Germain BF, Espinoza LR (1991) Prolactin, immunoregulation, and autoimmune diseases. Semin Arthritis Rheum 20(5):273–284PubMedGoogle Scholar
  55. 55.
    Jara LJ, Navarro C, Medina G, Vera-Lastra O, Blanco F (2006) Immune-neuroendocrine interactions and autoimmune diseases. Clin Dev Immunol 13(2–4):109–123. doi:10.1080/17402520600877059PubMedCentralPubMedGoogle Scholar
  56. 56.
    Jara LJ, Medina G, Saavedra M, Vera-Lastra O, Navarro C (2011) Prolactin and autoimmunity. Clinic Rev Allerg Immunol 40(1):50–59. doi:10.1007/s12016-009-8185-3Google Scholar
  57. 57.
    Kaufmann SHE, Medzhitov R, Gordon S (2004) The innate immune response to infection. ASM, Washington, DCGoogle Scholar
  58. 58.
    Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol 11(5):373–384. doi:10.1038/ni.1863PubMedGoogle Scholar
  59. 59.
    Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34(5):637–650. doi:10.1016/j.immuni.2011.05.006PubMedGoogle Scholar
  60. 60.
    Kelly PA, Djiane J, Postel-Vinay MC, Edery M (1991) The prolactin/growth hormone receptor family. Endocr Rev 12(3):235–251. doi:10.1210/edrv-12-3-235PubMedGoogle Scholar
  61. 61.
    Klein JR (2006) The immune system as a regulator of thyroid hormone activity. Exp Biol Med 231(3):229–236Google Scholar
  62. 62.
    Kline JB, Clevenger CV (2001) Identification and characterization of the prolactin-binding protein in human serum and milk. J Biol Chem 276(27):24760–24766. doi:10.1074/jbc.M011786200PubMedGoogle Scholar
  63. 63.
    Kline JB, Roehrs H, Clevenger CV (1999) Functional characterization of the intermediate isoform of the human prolactin receptor. J Biol Chem 274(50):35461–35468PubMedGoogle Scholar
  64. 64.
    Kline JB, Rycyzyn MA, Clevenger CV (2002) Characterization of a novel and functional human prolactin receptor isoform (deltaS1PRLr) containing only one extracellular fibronectin-like domain. Mol Endocrinol 16(10):2310–2322. doi:10.1210/me.2001-0033PubMedGoogle Scholar
  65. 65.
    Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388(4):621–625. doi:10.1016/j.bbrc.2009.08.062PubMedGoogle Scholar
  66. 66.
    Lahat N, Miller A, Shtiller R, Touby E (1993) Differential effects of prolactin upon activation and differentiation of human B lymphocytes. J Neuroimmunol 47(1):35–40PubMedGoogle Scholar
  67. 67.
    Lang TJ (2004) Estrogen as an immunomodulator. Clin Immunol 113(3):224–230. doi:10.1016/j.clim.2004.05.011PubMedGoogle Scholar
  68. 68.
    Lee SH, Kunz J, Lin SH, Yu-Lee LY (2007) 16-kDa prolactin inhibits endothelial cell migration by down-regulating the Ras-Tiam1-Rac1-Pak1 signaling pathway. Cancer Res 67(22):11045–11053. doi:10.1158/0008-5472.CAN-07-0986PubMedGoogle Scholar
  69. 69.
    Legorreta-Haquet MV, Chavez-Rueda K, Montoya-Diaz E, Arriaga-Pizano L, Silva-Garcia R, Chavez-Sanchez L, Moreno-Lafont M, Zenteno-Galindo E, Blanco-Favela F (2012) Prolactin down-regulates CD4+ CD25hiCD127low/- regulatory T cell function in humans. J Mol Endocrinol 48(1):77–85. doi:10.1530/JME-11-0040PubMedGoogle Scholar
  70. 70.
    Lopez-Rincon G, Gutierrez-Pabello JA, Diaz-Otero F, Munoz-Valle JF, Pereira-Suarez AL, Estrada-Chavez C (2013a) Mycobacterium bovis infection in cattle induces differential expression of prolactin receptor isoforms in macrophages. Comp Immunol Microbiol Infect Dis 36(6):619–629. doi:10.1016/j.cimid.2013.09.001PubMedGoogle Scholar
  71. 71.
    Lopez-Rincon G, Pereira-Suarez AL, Del Toro-ArreolaS, Sanchez-Hernandez PE, Ochoa-Zarzosa A, Munoz-Valle JF, Estrada-Chavez C (2013b) Lipopolysaccharide induces the expression of an autocrine prolactin loop enhancing inflammatory response in monocytes. J Inflamm (Lond) 10(1):24. doi:10.1186/1476-9255-10-24PubMedCentralGoogle Scholar
  72. 72.
    Lorton D, Lubahn CL, Zautra AJ, Bellinger DL (2008) Proinflammatory cytokines and sickness behavior in rheumatic diseases. Curr Pharm Des 14(13):1242–1260PubMedGoogle Scholar
  73. 73.
    Lovato P, Brender C, Agnholt J, Kelsen J, Kaltoft K, Svejgaard A, Eriksen KW, Woetmann A, Odum N (2003) Constitutive STAT3 activation in intestinal T cells from patients with Crohn’s disease. J Biol Chem 278(19):16777–16781. doi:10.1074/jbc.M207999200PubMedGoogle Scholar
  74. 74.
    Luo G, Yu-Lee L (1997) Transcriptional inhibition by Stat5. Differential activities at growth-related versus differentiation-specific promoters. J Biol Chem 272(43):26841–26849PubMedGoogle Scholar
  75. 75.
    Ma J, Chen T, Mandelin J, Ceponis A, Miller NE, Hukkanen M, Ma GF, Konttinen YT (2003) Regulation of macrophage activation. Cell Mol Life Sci 60(11):2334–2346. doi:10.1007/s00018-003-3020-0PubMedGoogle Scholar
  76. 76.
    Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13. doi:10.12703/P6-13PubMedCentralPubMedGoogle Scholar
  77. 77.
    Martini JF, Piot C, Humeau LM, Struman I, Martial JA, Weiner RI (2000) The antiangiogenic factor 16 K PRL induces programmed cell death in endothelial cells by caspase activation. Mol Endocrinol 14(10):1536–1549. doi:10.1210/mend.14.10.0543PubMedGoogle Scholar
  78. 78.
    Matalka KZ (2003) Prolactin enhances production of interferon-gamma, interleukin-12, and interleukin-10, but not of tumor necrosis factor-alpha, in a stimulus-specific manner. Cytokine 21(4):187–194PubMedGoogle Scholar
  79. 79.
    Matera L, Bellone G, Contarini M (1992a) Synthesis of a prolactin-like peptide by natural killer cells: positive regulation by CD16 and exogenous prolactin. Cell Mol Biol 38(8):915–920PubMedGoogle Scholar
  80. 80.
    Matera L, Cesano A, Bellone G, Oberholtzer E (1992b) Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes. Brain Behav Immun 6(4):409–417PubMedGoogle Scholar
  81. 81.
    Matera L, Contarini M, Bellone G, Forno B, Biglino A (1999) Up-modulation of interferon-gamma mediates the enhancement of spontanous cytotoxicity in prolactin-activated natural killer cells. Immunology 98(3):386–392PubMedCentralPubMedGoogle Scholar
  82. 82.
    Matera L, Galetto A, Geuna M, Vekemans K, Ricotti E, Contarini M, Moro F, Basso G (2000) Individual and combined effect of granulocyte-macrophage colony-stimulating factor and prolactin on maturation of dendritic cells from blood monocytes under serum-free conditions. Immunology 100(1):29–36PubMedCentralPubMedGoogle Scholar
  83. 83.
    Matera L, Mori M, Galetto A (2001) Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells. Lupus 10(10):728–734PubMedGoogle Scholar
  84. 84.
    Miller WL, Coit D, Baxter JD, Martial JA (1981) Cloning of bovine prolactin cDNA and evolutionary implications of its sequence. DNA 1(1):37–50PubMedGoogle Scholar
  85. 85.
    Moderscheim TA, Gorba T, Pathipati P, Kokay IC, Grattan DR, Williams CE, Scheepens A (2007) Prolactin is involved in glial responses following a focal injury to the juvenile rat brain. Neuroscience 145(3):963–973. doi:10.1016/j.neuroscience.2006.12.053PubMedGoogle Scholar
  86. 86.
    Mogensen TH (2009) Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22(2):240–273. doi:10.1128/CMR.00046-08PubMedCentralPubMedGoogle Scholar
  87. 87.
    Monasterio N, Vergara E, Morales T (2013) Hormonal influences on neuroimmune responses in the CNS of females. Front Integ Neurosci 7:110. doi:10.3389/fnint.2013.00110Google Scholar
  88. 88.
    Morales P, Carretero MV, Geronimo H, Copin SG, Gaspar ML, Marcos MA, Martin-Perez J (1999) Influence of prolactin on the differentiation of mouse B-lymphoid precursors. Cell Growth Differ 10(8):583–590PubMedGoogle Scholar
  89. 89.
    Moser B, Loetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2(2):123–128. doi:10.1038/84219PubMedGoogle Scholar
  90. 90.
    Murakami Y, Miyake K (2012) [Innate immune responses and inflammatory diseases via NLR-inflammasome]. Nihon Rinsho 70(Suppl 8):242–245PubMedGoogle Scholar
  91. 91.
    Nagy E, Berczi I (1978) Immunodeficiency in hypophysectomized rats. Acta Endocrinol 89(3):530–537PubMedGoogle Scholar
  92. 92.
    Nagy E, Berczi I (1991) Hypophysectomized rats depend on residual prolactin for survival. Endocrinology 128(6):2776–2784. doi:10.1210/endo-128-6-2776PubMedGoogle Scholar
  93. 93.
    Nimura F, Zhang LF, Okuma K, Tanaka R, Sunakawa H, Yamamoto N, Tanaka Y (2006) Cross-linking cell surface chemokine receptors leads to isolation, activation, and differentiation of monocytes into potent dendritic cells. Exp Biol Med 231(4):431–443Google Scholar
  94. 94.
    Olavarria VH, Sepulcre MP, Figueroa JE, Mulero V (2010) Prolactin-induced production of reactive oxygen species and IL-1beta in leukocytes from the bony fish gilthead seabream involves Jak/Stat and NF-kappaB signaling pathways. J Immunol 185(7):3873–3883. doi:10.4049/jimmunol.0902306PubMedGoogle Scholar
  95. 95.
    Ormandy CJ, Binart N, Helloco C, Kelly PA (1998) Mouse prolactin receptor gene: genomic organization reveals alternative promoter usage and generation of isoforms via alternative 3'-exon splicing. DNA Cell Biol 17(9):761–770PubMedGoogle Scholar
  96. 96.
    Ospelt C, Gay S (2010) TLRs and chronic inflammation. Int J Biochem Cell Biol 42(4):495–505. doi:10.1016/j.biocel.2009.10.010PubMedGoogle Scholar
  97. 97.
    Pan W, Yu C, Hsuchou H, Zhang Y, Kastin AJ (2008) Neuroinflammation facilitates LIF entry into brain: role of TNF. Am J Physiol Cell Physiol 294(6):C1436–C1442. doi:10.1152/ajpcell.00489.2007PubMedCentralPubMedGoogle Scholar
  98. 98.
    Paredes M, Gonzalez K, Figueroa J, Montiel-Eulefi E (2013) Immunomodulatory effect of prolactin on Atlantic salmon (Salmo salar) macrophage function. Fish Physiol Biochem 39(5):1215–1221. doi:10.1007/s10695-013-9777-7PubMedGoogle Scholar
  99. 99.
    Paul S, Biswas A, Sasmal K, Mukherjee S, Biswas T, Biswas R (2010) IL-10 alters prolactin receptor activity emulating that during breast cancer. Cytokine 51(2):144–150. doi:10.1016/j.cyto.2010.04.012PubMedGoogle Scholar
  100. 100.
    Peeva E, Grimaldi C, Spatz L, Diamond B (2000) Bromocriptine restores tolerance in estrogen-treated mice. J Clin Invest 106(11):1373–1379. doi:10.1172/JCI10420PubMedCentralPubMedGoogle Scholar
  101. 101.
    Pellegrini I, Lebrun JJ, Ali S, Kelly PA (1992) Expression of prolactin and its receptor in human lymphoid cells. Mol Endocrinol 6(7):1023–1031. doi:10.1210/mend.6.7.1508218PubMedGoogle Scholar
  102. 102.
    Piwnica D, Touraine P, Struman I, Tabruyn S, Bolbach G, Clapp C, Martial JA, Kelly PA, Goffin V (2004) Cathepsin D processes human prolactin into multiple 16 K-like N-terminal fragments: study of their antiangiogenic properties and physiological relevance. Mol Endocrinol 18(10):2522–2542. doi:10.1210/me.2004-0200PubMedGoogle Scholar
  103. 103.
    Plocinski P, Dzitko K, Dlugonska H (2007) [Prolactin as a modulator of antiparasitic immunity]. Wiad Parazytol 53(4):263–270PubMedGoogle Scholar
  104. 104.
    Reber PM (1993) Prolactin and immunomodulation. Am J Med 95(6):637–644PubMedGoogle Scholar
  105. 105.
    Redelman D, Welniak LA, Taub D, Murphy WJ (2008) Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network. Cell Immunol 252(1–2):111–121. doi:10.1016/j.cellimm.2007.12.003PubMedGoogle Scholar
  106. 106.
    Rentier-Delrue F, Swennen D, Prunet P, Lion M, Martial JA (1989) Tilapia prolactin: molecular cloning of two cDNAs and expression in Escherichia coli. DNA 8(4):261–270PubMedGoogle Scholar
  107. 107.
    Riddle O, Bates R, Dykshorn SW (1933) The preparation, identification and assay of prolactin—a hormone of the anterior pituitary. AmJ Physiol 105:191–216Google Scholar
  108. 108.
    Romanovsky AA, Blatteis CM (2000) Heat defense control in an experimental heat disorder. Int J Biometeorol 43(4):172–175PubMedGoogle Scholar
  109. 109.
    Romero A, Manriquez R, Alvarez C, Gajardo C, Vasquez J, Kausel G, Monras M, Olavarria VH, Yanez A, Enriquez R, Figueroa J (2012) Prolactin-releasing peptide is a potent mediator of the innate immune response in leukocytes from Salmo salar. Vet Immunol Immunopathol 147(3–4):170–179. doi:10.1016/j.vetimm.2012.04.014PubMedGoogle Scholar
  110. 110.
    Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Arkins S, Kooijman R, Kutz L, Kelley KW, Malarkey WB (1992) Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation. Proc Natl Acad Sci U S A 89(16):7713–7716PubMedCentralPubMedGoogle Scholar
  111. 111.
    Scotland PE, Patil M, Belugin S, Henry MA, Goffin V, Hargreaves KM, Akopian AN (2011a) Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia. Eur J Neurosci 34(5):745–754. doi:10.1111/j.1460-9568.2011.07788.xPubMedCentralPubMedGoogle Scholar
  112. 112.
    Scotland RS, Stables MJ, Madalli S, Watson P, Gilroy DW (2011b) Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood 118(22):5918–5927. doi:10.1182/blood-2011-03-340281PubMedGoogle Scholar
  113. 113.
    Schroeder MD, Symowicz J, Schuler LA (2002) PRL modulates cell cycle regulators in mammary tumor epithelial cells. Mol Endocrinol 16(1):45–57. doi:10.1210/mend.16.1.0762PubMedGoogle Scholar
  114. 114.
    Serhan CN, Ward PA, Gilroy DW (2010) Fundamentals of inflammation. Cambridge University Press, CambridgeGoogle Scholar
  115. 115.
    Sinha YN (1995) Structural variants of prolactin: Occurrence and physiological significance. Endocr Rev 16(3):354–369. doi:10.1210/edrv-16-3-354PubMedGoogle Scholar
  116. 116.
    Sodhi A, Tripathi A (2008a) Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB. Cytokine 41(2):162–173. doi:10.1016/j.cyto.2007.11.007PubMedGoogle Scholar
  117. 117.
    Sodhi A, Tripathi A (2008b) Prolactin induced production of cytokines in macrophages involves Ca++ and p42/44 MAP kinase signaling pathway. Growth Factors 26(4):212–219. doi:10.1080/08977190802273830PubMedGoogle Scholar
  118. 118.
    Steinman L (2004a) Elaborate interactions between the immune and nervous systems. Nat Immunol 5(6):575–581. doi:10.1038/ni1078PubMedGoogle Scholar
  119. 119.
    Steinman L (2004b) Immune therapy for autoimmune diseases. Science 305(5681):212–216. doi:10.1126/science.1099896PubMedGoogle Scholar
  120. 120.
    Stevens AM, Wang YF, Sieger KA, Lu HF, Yu-Lee LY (1995) Biphasic transcriptional regulation of the interferon regulatory factor-1 gene by prolactin: involvement of gamma-interferon-activated sequence and Stat-related proteins. Mol Endocrinol 9(4):513–525. doi:10.1210/mend.9.4.7659094PubMedGoogle Scholar
  121. 121.
    Stricker P, Grueter R (1928) Action du lobe ante´rieur de l’hypophyse sur la monte´e laiteuse. Compt rend Soc de Biol 99:1978–1980Google Scholar
  122. 122.
    Tabruyn SP, Sorlet CM, Rentier-Delrue F, Bours V, Weiner RI, Martial JA, Struman I (2003) The antiangiogenic factor 16 K human prolactin induces caspase-dependent apoptosis by a mechanism that requires activation of nuclear factor-kappaB. Mol Endocrinol 17(9):1815–1823. doi:10.1210/me.2003-0132PubMedGoogle Scholar
  123. 123.
    Tabruyn SP, Nguyen NQ, Cornet AM, Martial JA, Struman I (2005) The antiangiogenic factor, 16-kDa human prolactin, induces endothelial cell cycle arrest by acting at both the G0-G1 and the G2-M phases. Mol Endocrinol 19(7):1932–1942. doi:10.1210/me.2004-0515PubMedGoogle Scholar
  124. 124.
    Takizawa K, Kitani S, Takeuchi F, Yamamoto K (2005) Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells by prolactin. Endocr J 52(5):635–641PubMedGoogle Scholar
  125. 125.
    Tan D, Huang KT, Ueda E, Walker AM (2008) S2 deletion variants of human PRL receptors demonstrate that extracellular domain conformation can alter conformation of the intracellular signaling domain. BioChemistry 47(1):479–489. doi:10.1021/bi7013882PubMedCentralPubMedGoogle Scholar
  126. 126.
    Tang MW, Reedquist KA, Garcia S, Gerlag DM, PP. T (2014) Prolactin is locally produced in the synovium of patients with inflammatory arthritic diseases and promotes macrophage activation. Ann Rheum Dis 1 (73(Suppl 1):A24–A25. doi: 10.1136/annrheumdis-2013-205124.56. PubMed PMID: 24489173Google Scholar
  127. 127.
    Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S (2005) Macrophage receptors and immune recognition. Annu Rev Immunol 23:901–944. doi:10.1146/annurev.immunol.23.021704.115816PubMedGoogle Scholar
  128. 128.
    Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB (2005) Solution structure of human prolactin. J Mol Biol 351(4):810–823. doi:10.1016/j.jmb.2005.06.042PubMedGoogle Scholar
  129. 129.
    Tomio A, Schust DJ, Kawana K, Yasugi T, Kawana Y, Mahalingaiah S, Fujii T, Taketani Y (2008) Prolactin can modulate CD4+ T-cell response through receptor-mediated alterations in the expression of T-bet. Immunol Cell Biol 86(7):616–621. doi:10.1038/icb.2008.29PubMedGoogle Scholar
  130. 130.
    Tracey K (2002) The inflammatory reflex. Nature 420(6917):853–859PubMedGoogle Scholar
  131. 131.
    Tripathi A, Sodhi A (2007) Production of nitric oxide by murine peritoneal macrophages in vitro on treatment with prolactin and growth hormone: involvement of protein tyrosine kinases, Ca(++), and MAP kinase signal transduction pathways. Mol Immunol 44(12):3185–3194. doi:10.1016/j.molimm.2007.01.024PubMedGoogle Scholar
  132. 132.
    Tripathi A, Sodhi A (2008) Prolactin-induced production of cytokines in macrophages in vitro involves JAK/STAT and JNK MAPK pathways. Int Immunol 20(3):327–336. doi:10.1093/intimm/dxm145PubMedGoogle Scholar
  133. 133.
    Trott JF, Hovey RC, Koduri S, Vonderhaar BK (2003) Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol 30(1):31–47PubMedGoogle Scholar
  134. 134.
    Walker AM (1994) Phosphorylated and nonphosphorylated Prolactin isoforms. Trends Endocrinol Metab 5(5):195–200PubMedGoogle Scholar
  135. 135.
    Weigent DA, Blalock JE (1987) Interactions between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev 100:79–108PubMedGoogle Scholar
  136. 136.
    Wells JA, de Vos AM (1996) Hematopoietic receptor complexes. Annu Rev Biochem 65:609–634. doi:10.1146/ Scholar
  137. 137.
    Williams LM, Sarma U, Willets K, Smallie T, Brennan F, Foxwell BM (2007) Expression of constitutively active STAT3 can replicate the cytokine-suppressive activity of interleukin-10 in human primary macrophages. J Biol Chem 282(10):6965–6975. doi:10.1074/jbc.M609101200PubMedGoogle Scholar
  138. 138.
    Xu D, Lin L, Lin X, Huang Z, Lei Z (2010) Immunoregulation of autocrine prolactin: suppressing the expression of costimulatory molecules and cytokines in T lymphocytes by prolactin receptor knockdown. Cell Immunol 263(1):71–78. doi:10.1016/j.cellimm.2010.02.018PubMedGoogle Scholar
  139. 139.
    Yu-Lee LY (2002) Prolactin modulation of immune and inflammatory responses. Recent Prog Horm Res 57:435–455PubMedGoogle Scholar
  140. 140.
    Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9(11):798–809. doi:10.1038/nrc2734PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ana Laura Pereira Suarez
    • 1
  • Gonzalo López-Rincón
    • 2
    • 3
  • Priscila A. Martínez Neri
    • 1
    • 2
  • Ciro Estrada-Chávez
    • 2
    Email author
  1. 1.Departamento de Fisiología, Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico
  2. 2.Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A. C., Av.GuadalajaraMéxico
  3. 3.Departamento de Investigación y Desarrollo Laboratorios Virbac América LatinaGuadalajaraMéxico

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