Abstract
The innate immune system of the lung is a complex network of different cellular and noncellular components protecting the lung from inhaled pathogens. Antimicrobial peptides (AMP) are produced by epithelial and myeloid cells as part of this system. AMPs, such as defensins and cathelicidin, are small cationic peptides with a broad microbicidal activity against respiratory bacteria, viruses, and fungi. However, their functions go beyond antimicrobial activity and include modulation of the innate and adaptive immune response to infection as well as lung repair after injury. Thus, AMPs are involved in pathophysiological processes of many lung diseases, such as acute and chronic lung infection, chronic obstructive pulmonary disease, cystic fibrosis, and lung cancer.
Keywords
- Chronic Obstructive Pulmonary Disease
- Cystic Fibrosis
- Respiratory Syncytial Virus
- Chronic Obstructive Pulmonary Disease Patient
- Alveolar Macrophage
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Aarbiou J, Ertmann M, van Wetering S et al (2002) Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J Leukoc Biol 72:167–174
Aarbiou J, Verhoosel RM, Van Wetering S et al (2004) Neutrophil defensins enhance lung epithelial wound closure and mucin gene expression in vitro. Am J Respir Cell Mol Biol 30:193–201
Aerts AM, François IEJA, Cammue BPA, Thevissen K (2008) The mode of antifungal action of plant, insect and human defensins. Cell Mol Life Sci 65:2069–2079
Agerberth B, Grunewald J, Castaños-Velez E et al (1999) Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients. Am J Respir Crit Care Med 160:283–290
Akira S (2009) Pathogen recognition by innate immunity and its signaling. Proc Jpn Acad Ser B Phys Biol Sci 85:143–156
Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801
Alalwani SM, Sierigk J, Herr C et al (2010) The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol 40:1118–1126
Albanesi C, Fairchild HR, Madonna S et al (2007) IL-4 and IL-13 negatively regulate TNF-alpha- and IFN-gamma-induced beta-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. J Immunol 179:984–992
Alekseeva L, Huet D, Féménia F et al (2009) Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms. BMC Microbiol 9:33
Arimura Y, Ashitani J, Yanagi S et al (2004) Elevated serum beta-defensins concentrations in patients with lung cancer. Anticancer Res 24:4051–4057
Bals R, Wang X, Wu Z et al (1998a) Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102:874–880
Bals R, Wang X, Zasloff M, Wilson JM (1998b) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A 95:9541–9546
Bals R, Weiner DJ, Meegalla RL, Wilson JM (1999) Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. J Clin Invest 103:1113–1117
Bals R, Weiner DJ, Meegalla RL et al (2001) Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid. Am J Respir Cell Mol Biol 25:21–25
Beisswenger C, Bals R (2005) Antimicrobial peptides in lung inflammation. Chem Immunol Allergy 86:55–71
Benincasa M, Mattiuzzo M, Herasimenka Y et al (2009) Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens. J Pept Sci 15:595–600
Bhat S, Song Y-H, Lawyer C, Milner SM (2007) Modulation of the complement system by human beta-defensin 2. J Burns Wounds 5, e10
Biragyn A, Ruffini PA, Leifer CA et al (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025–1029
Boniotto M, Jordan WJ, Eskdale J et al (2006) Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother 50:1433–1441
Bowdish DME, Davidson DJ, Speert DP, Hancock REW (2004) The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol 172:3758–3765
Bowdish DME, Davidson DJ, Lau YE et al (2005) Impact of LL-37 on anti-infective immunity. J Leukoc Biol 77:451–459. doi:10.1189/jlb.0704380
Braff MH, Jones AL, Skerrett SJ, Rubens CE (2007) Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. J Infect Dis 195:1365–1372
Byfield FJ, Kowalski M, Cruz K et al (2011) Cathelicidin LL-37 increases lung epithelial cell stiffness, decreases transepithelial permeability, and prevents epithelial invasion by Pseudomonas aeruginosa. J Immunol 187:6402–6409
Campbell EL, Serhan CN, Colgan SP (2011) Antimicrobial aspects of inflammatory resolution in the mucosa: a role for proresolving mediators. J Immunol 187:3475–3481
Carretero M, Escámez MJ, García M et al (2008) In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 128:223–236
Chen CI-U, Schaller-Bals S, Paul KP et al (2004) Beta-defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic fibrosis. J Cyst Fibros 3:45–50
Chen X, Niyonsaba F, Ushio H et al (2005) Synergistic effect of antibacterial agents human beta-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli. J Dermatol Sci 40:123–132
Chertov O, Michiel DF, Xu L et al (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 271:2935–2940
Chong KT, Thangavel RR, Tang X (2008) Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice. Virology 380:136–143
Cowland JB, Johnsen AH, Borregaard N (1995) hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett 368:173–176
Dauletbaev N, Gropp R, Frye M et al (2002) Expression of human beta defensin (HBD-1 and HBD-2) mRNA in nasal epithelia of adult cystic fibrosis patients, healthy individuals, and individuals with acute cold. Respir Int Rev Thorac Dis 69:46–51
Davidson DJ, Currie AJ, Reid GSD et al (2004) The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 172:1146–1156
Di Nardo A, Vitiello A, Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170:2274–2278
Doss M, White MR, Tecle T, Hartshorn KL (2010) Human defensins and LL-37 in mucosal immunity. J Leukoc Biol 87:79–92
Duits LA, Ravensbergen B, Rademaker M et al (2002) Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106:517–525
Duits LA, Nibbering PH, van Strijen E et al (2003) Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol 38:59–64
Felgentreff K, Beisswenger C, Griese M et al (2006) The antimicrobial peptide cathelicidin interacts with airway mucus. Peptides 27:3100–3106
Filewod NCJ, Pistolic J, Hancock REW (2009) Low concentrations of LL-37 alter IL-8 production by keratinocytes and bronchial epithelial cells in response to proinflammatory stimuli. FEMS Immunol Med Microbiol 56:233–240
Froy O (2005) Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways. Cell Microbiol 7:1387–1397
Frye M, Bargon J, Dauletbaev N et al (2000) Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells. J Clin Pathol 53:770–773
Funderburg N, Lederman MM, Feng Z et al (2007) Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A 104:18631–18635
Funderburg NT, Jadlowsky JK, Lederman MM et al (2011) The toll-like receptor 1/2 agonists Pam(3) CSK(4) and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes. Immunology 134:151–160
Futosi K, Fodor S, Mócsai A (2013) Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol 17:638–650
Ganz T, Selsted ME, Szklarek D et al (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427–1435
García JR, Krause A, Schulz S et al (2001) Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 15:1819–1821
Garmendia J, Morey P, Bengoechea JA (2012) Impact of cigarette smoke exposure on host-bacterial pathogen interactions. Eur Respir J 39:467–477
Goldman MJ, Anderson GM, Stolzenberg ED et al (1997) Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553–560
Gombart AF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 19:1067–1077
Han W, Wang W, Mohammed KA, Su Y (2009) Alpha-defensins increase lung fibroblast proliferation and collagen synthesis via the beta-catenin signaling pathway. FEBS J 276:6603–6614
Hancock REW, Scott MG (2000) The role of antimicrobial peptides in animal defenses. Proc Natl Acad Sci 97:8856–8861
Hansdottir S, Monick MM, Hinde SL et al (2008) Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 181:7090–7099
Harder J, Meyer-Hoffert U, Teran LM et al (2000) Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol 22:714–721
Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713
Heilborn JD, Nilsson MF, Kratz G et al (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120:379–389
Herr C, Beisswenger C, Hess C et al (2009) Suppression of pulmonary innate host defence in smokers. Thorax 64:144–149
Hertz CJ, Wu Q, Porter EM et al (2003) Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol 171:6820–6826
Hess C, Herr C, Beisswenger C et al (2010) Myeloid RelA regulates pulmonary host defense networks. Eur Respir J 35:343–352
Hiratsuka T, Nakazato M, Date Y et al (1998) Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia. Biochem Biophys Res Commun 249:943–947
Hiratsuka T, Mukae H, Iiboshi H et al (2003) Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 58:425–430
Hou M, Zhang N, Yang J et al (2013) Antimicrobial peptide LL-37 and IDR-1 ameliorate MRSA pneumonia in vivo. Cell Physiol Biochem 32:614–623
Hu Q, Zuo P, Shao B et al (2010) Administration of nonviral gene vector encoding rat beta-defensin-2 ameliorates chronic Pseudomonas aeruginosa lung infection in rats. J Gene Med 12:276–286
Ishimoto H, Mukae H, Date Y et al (2006) Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia. Eur Respir J 27:253–260
Iwase T, Uehara Y, Shinji H et al (2010) Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465:346–349
Jin T, Bokarewa M, Foster T et al (2004) Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol 172:1169–1176
Kandler K, Shaykhiev R, Kleemann P et al (2006) The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. Int Immunol 18:1729–1736
Kao CY, Chen Y, Zhao YH, Wu R (2003) ORFeome-based search of airway epithelial cell-specific novel human [beta]-defensin genes. Am J Respir Cell Mol Biol 29:71–80
Kao C-Y, Chen Y, Thai P et al (2004) IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol 173:3482–3491
Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:464
Khine AA, Del Sorbo L, Vaschetto R et al (2006) Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 107:2936–2942
Kirikae T, Hirata M, Yamasu H et al (1998) Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia. Infect Immun 66:1861–1868
Klotman ME, Chang TL (2006) Defensins in innate antiviral immunity. Nat Rev Immunol 6:447–456
Klugman KP, Garau J (2009) A preventable killer: pneumonia. Clin Microbiol Infect 15:989–990
Koczulla R, von Degenfeld G, Kupatt C et al (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672
Koeffler HP, Reichel H, Bishop JE, Norman AW (1985) gamma-Interferon stimulates production of 1,25-dihydroxyvitamin D3 by normal human macrophages. Biochem Biophys Res Commun 127:596–603
Kota S, Sabbah A, Chang TH et al (2008) Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappaB-mediated innate antiviral response against human respiratory syncytial virus. J Biol Chem 283:22417–22429
Kovach MA, Standiford TJ (2011) Toll like receptors in diseases of the lung. Int Immunopharmacol 11:1399–1406
Kovach MA, Ballinger MN, Newstead MW et al (2012) Cathelicidin-related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. J Immunol 189:304–311
Kulkarni R, Rampersaud R, Aguilar JL et al (2010) Cigarette smoke inhibits airway epithelial cell innate immune responses to bacteria. Infect Immun 78:2146–2152
Kurosaka K, Chen Q, Yarovinsky F et al (2005) Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J Immunol 174:6257–6265
Kusagaya H, Fujisawa T, Yamanaka K et al (2014) Toll-like receptor-mediated airway IL-17C enhances epithelial host defense in an autocrine/paracrine manner. Am J Respir Cell Mol Biol 50:30–39
Laan M, Bozinovski S, Anderson GP (2004) Cigarette smoke inhibits lipopolysaccharide-induced production of inflammatory cytokines by suppressing the activation of activator protein-1 in bronchial epithelial cells. J Immunol 173:4164–4170
Lai Y, Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30:131–141
Lai Y, Adhikarakunnathu S, Bhardwaj K et al (2011) LL37 and cationic peptides enhance TLR3 signaling by viral double-stranded RNAs. PLoS One 6, e26632
Larrick J, Hirata M, Balint R et al (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63:1291–1297
Li D, Beisswenger C, Herr C et al (2014) Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth. Oncogene 33:2709–2716
Liao Z, Dong J, Hu X et al (2012) Enhanced expression of human β-defensin 2 in peripheral lungs of patients with chronic obstructive pulmonary disease. Peptides 38:350–356
Lichtenstein A (1991) Mechanism of mammalian cell lysis mediated by peptide defensins. Evidence for an initial alteration of the plasma membrane. J Clin Invest 88:93–100
Liu PT, Stenger S, Li H et al (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770–1773
MacRedmond R, Greene C, Taggart CC et al (2005) Respiratory epithelial cells require Toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide. Respir Res 6:116
McCray PB, Bentley L (1997) Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 16:343–349
Mehta H, Nazzal K, Sadikot RT (2008) Cigarette smoking and innate immunity. Inflamm Res 57:497–503
Méndez-Samperio P, Alba L, Trejo A (2007) Mycobacterium bovis-mediated induction of human beta-defensin-2 in epithelial cells is controlled by intracellular calcium and p38MAPK. J Infect 54:469–474
Merkel D, Rist W, Seither P et al (2005) Proteomic study of human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification. Proteomics 5:2972–2980
Michelson PH, Tigue M, Panos RJ, Sporn PH (1999) Keratinocyte growth factor stimulates bronchial epithelial cell proliferation in vitro and in vivo. Am J Physiol 277:L737–L742
Miles K, Clarke DJ, Lu W et al (2009) Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol 183:2122–2132
Mitsudomi T, Yatabe Y (2010) Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 277:301–308
Moghaddam SJ, Ochoa CE, Sethi S, Dickey BF (2011) Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer. Int J Chron Obstruct Pulmon Dis 6:113–123
Mookherjee N, Brown KL, Bowdish DME et al (2006) Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 176:2455–2464
Moser C, Weiner DJ, Lysenko E et al (2002) beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 70:3068–3072
Mukae H, Iiboshi H, Nakazato M et al (2002) Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis. Thorax 57:623–628
Murphy CJ, Foster BA, Mannis MJ et al (1993) Defensins are mitogenic for epithelial cells and fibroblasts. J Cell Physiol 155:408–413
Nijnik A, Pistolic J, Filewod NCJ, Hancock REW (2012) Signaling pathways mediating chemokine induction in keratinocytes by cathelicidin LL-37 and flagellin. J Innate Immun 4:377–386
Niyonsaba F (2002) Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol 14:421–426
Niyonsaba F, Someya A, Hirata M et al (2001) Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur J Immunol 31:1066–1075
Niyonsaba F, Iwabuchi K, Someya A et al (2002) A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106:20–26
O’Neil DA, Porter EM, Elewaut D et al (1999) Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 163:6718–6724
Okrent DG, Lichtenstein AK, Ganz T (1990) Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells. Am Rev Respir Dis 141:179–185
Pace E, Ferraro M, Minervini MI et al (2012) Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients. PLoS One 7, e33601
Parker D, Prince A (2011) Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol 45:189–201
Pingel LC, Kohlgraf KG, Hansen CJ et al (2008) Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response. Immunol Cell Biol 86:643–649
Pistolic J, Cosseau C, Li Y et al (2009) Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway. J Innate Immun 1:254–267
Platz J, Beisswenger C, Dalpke A et al (2004) Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J Immunol 173:1219–1223
Proud D, Sanders SP, Wiehler S (2004) Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J Immunol 172:4637–4645
Puddicombe SM, Polosa R, Richter A et al (2000) Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J 14:1362–1374
Rivas-Santiago B, Schwander SK, Sarabia C et al (2005) Human {beta}-defensin 2 is expressed and associated with Mycobacterium tuberculosis during infection of human alveolar epithelial cells. Infect Immun 73:4505–4511
Rivas-Santiago B, Hernandez-Pando R, Carranza C et al (2008) Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infect Immun 76:935–941
Röhrl J, Yang D, Oppenheim JJ, Hehlgans T (2010) Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 184:6688–6694
Ross DJ, Cole AM, Yoshioka D et al (2004) Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation. Transplantation 78:1222–1224
Saiman L, Tabibi S, Starner TD et al (2001) Cathelicidin peptides inhibit multiply antibiotic-resistant pathogens from patients with cystic fibrosis. Antimicrob Agents Chemother 45:2838–2844
Sakamoto N, Mukae H, Fujii T et al (2005) Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 288:L508–L513
Schaller-Bals S, Schulze A, Bals R (2002) Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection. Am J Respir Crit Care Med 165:992–995
Scharf S, Vardarova K, Lang F et al (2010a) Legionella pneumophila induces human beta defensin-3 in pulmonary cells. Respir Res 11:93
Scharf S, Hippenstiel S, Flieger A et al (2010b) Induction of human β-defensin-2 in pulmonary epithelial cells by Legionella pneumophila: involvement of TLR2 and TLR5, p38 MAPK, JNK, NF-κB, and AP-1. Am J Physiol Lung Cell Mol Physiol 298:L687–L695
Scharf S, Zahlten J, Szymanski K et al (2012) Streptococcus pneumoniae induces human β-defensin-2 and -3 in human lung epithelium. Exp Lung Res 38:100–110
Schauber J, Dorschner RA, Coda AB et al (2007a) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117:803–811
Schauber J, Oda Y, Büchau AS et al (2007b) Histone acetylation in keratinocytes enables control of the expression of cathelicidin and CD14 by 1,25-dihydroxyvitamin D3. J Invest Dermatol 128:816–824
Schiemann F, Brandt E, Gross R et al (2009) The cathelicidin LL-37 activates human mast cells and is degraded by mast cell tryptase: counter-regulation by CXCL4. J Immunol 183:2223–2231
Scott MG, Gold MR, Hancock RE (1999a) Interaction of cationic peptides with lipoteichoic acid and gram-positive bacteria. Infect Immun 67:6445–6453
Scott MG, Yan H, Hancock REW (1999b) Biological properties of structurally related alpha -helical cationic antimicrobial peptides. Infect Immun 67:2005–2009
Scott MG, Vreugdenhil AC, Buurman WA et al (2000) Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J Immunol 164:549–553
Scott MG, Davidson DJ, Gold MR et al (2002) The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 169:3883–3891
Scott A, Weldon S, Buchanan PJ et al (2011) Evaluation of the ability of LL-37 to neutralise LPS in vitro and ex vivo. PLoS One 6, e26525
Seiler F, Hellberg J, Lepper PM et al (2013) FOXO transcription factors regulate innate immune mechanisms in respiratory epithelial cells. J Immunol 190:1603–1613
Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557
Semple F, Webb S, Li H-N et al (2010) Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol 40:1073–1078
Semple F, MacPherson H, Webb S et al (2011) Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF. Eur J Immunol 41:3291–3300
Sethi S (2010) Infection as a comorbidity of COPD. Eur Respir J 35:1209–1215
Sethi S, Murphy TF (2008) Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 359:2355–2365
Shaykhiev R, Beisswenger C, Kändler K et al (2005) Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am J Physiol Lung Cell Mol Physiol 289:L842–L848
Shaykhiev R, Sierigk J, Herr C et al (2010) The antimicrobial peptide cathelicidin enhances activation of lung epithelial cells by LPS. FASEB J 24:4756–4766
Shestakova T, Zhuravel E, Bolgova L et al (2008) Expression of human beta-defensins-1, 2 and 4 mRNA in human lung tumor tissue: a pilot study. Exp Oncol 30:153–156
Shu Q, Shi Z, Zhao Z et al (2006) Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats. Shock 26:365–371
Singh PK, Jia HP, Wiles K et al (1998) Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A 95:14961–14966
Soong LB, Ganz T, Ellison A, Caughey GH (1997) Purification and characterization of defensins from cystic fibrosis sputum. Inflamm Res 46:98–102
Soruri A, Grigat J, Forssmann U et al (2007) beta-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur J Immunol 37:2474–2486
Steinstraesser L, Koehler T, Jacobsen F et al (2008) Host defense peptides in wound healing. Mol Med 14:528–537
Sun C, Zhu M, Yang Z et al (2014) LL-37 secreted by epithelium promotes fibroblast collagen production: a potential mechanism of small airway remodeling in chronic obstructive pulmonary disease. Lab Invest 94:991–1002
Tjabringa GS, Aarbiou J, Ninaber DK et al (2003) The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 171:6690–6696
Tokumaru S, Sayama K, Shirakata Y et al (2005) Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 175:4662–4668
Tripathi S, Tecle T, Verma A et al (2013) The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins. J Gen Virol 94:40–49
Van Wetering S, Mannesse-Lazeroms SP, Dijkman JH, Hiemstra PS (1997) Effect of neutrophil serine proteinases and defensins on lung epithelial cells: modulation of cytotoxicity and IL-8 production. J Leukoc Biol 62:217–226
Vandamme D, Landuyt B, Luyten W, Schoofs L (2012) A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol 280:22–35
Varsano S, Kaminsky M, Kaiser M, Rashkovsky L (2000) Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line. Thorax 55:364–369
Von Haussen J, Koczulla R, Shaykhiev R et al (2008) The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells. Lung Cancer 59:12–23
Wang X, Zhang Z, Louboutin J-P et al (2003) Airway epithelia regulate expression of human beta-defensin 2 through Toll-like receptor 2. FASEB J 17:1727–1729
Wang T-T, Nestel FP, Bourdeau V et al (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909–2912
Wehkamp J, Harder J, Wehkamp K et al (2004) NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun 72:5750–5758
Xiong YQ, Yeaman MR, Bayer AS (1999) In vitro antibacterial activities of platelet microbicidal protein and neutrophil defensin against Staphylococcus aureus are influenced by antibiotics differing in mechanism of action. Antimicrob Agents Chemother 43:1111–1117
Xu N, Wang Y-S, Pan W-B et al (2008) Human alpha-defensin-1 inhibits growth of human lung adenocarcinoma xenograft in nude mice. Mol Cancer Ther 7:1588–1597
Yanagi S, Ashitani J, Ishimoto H et al (2005) Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection. Respir Res 6:130
Yang D, Chertov O, Bykovskaia SN et al (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528
Yang D, Chen Q, Chertov O, Oppenheim JJ (2000a) Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 68:9–14
Yang D, Chen Q, Schmidt AP et al (2000b) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069–1074
Yang D, Chertov O, Oppenheim JJ (2001) Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J Leukoc Biol 69:691–697
Ye P, Garvey PB, Zhang P et al (2001) Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am J Respir Cell Mol Biol 25:335–340
Yu J, Mookherjee N, Wee K et al (2007) Host defense peptide LL-37, in synergy with inflammatory mediator IL-1beta, augments immune responses by multiple pathways. J Immunol 179:7684–7691
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Seiler, F., Bals, R., Beisswenger, C. (2016). Function of Antimicrobial Peptides in Lung Innate Immunity. In: Harder, J., Schröder, JM. (eds) Antimicrobial Peptides. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-24199-9_3
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