Abstract
Human β-defensin-2(HBD-2) is one of the two major vertebrate antimicrobial peptide families (α and β), which is highly expressed by proinflammatory induction in the lung and exhibit broad-spectrum antimicrobial activity. We observed that IL-22 receptors high expressed on the membrane of A549 cells; HBD-2 mRNA was expressed in a time- and concentration-dependent manners in A549 cells when treated with IL-22; further studies demonstrated that HBD-2 expression was attenuated by AG490, but to JSH-23, inhibitors of p-STAT3 DNA binding and NF-κB/ p65 subunit nuclear translocation, respectively. These results support that IL-22-mediated signalling pathway of HBD-2 gene expression involved STAT3 but not NF-κB in human alveolar epithelium. These findings provide a new insight into how IL-22 may play an important link between innate and adaptive immunity, thereby anti-infection locally in the alveolar epithelium.
Similar content being viewed by others
Abbreviations
- IL:
-
Interleukin
- HBD:
-
Human β-defensin
- TBE:
-
Tracheobronchialepithelial
- AMPs:
-
Antimicrobial peptides
- IFN-γ:
-
Interferon-γ
- GM-CSF:
-
Granulocyte-macrophage colony-stimulatingfactor
- TNF-α:
-
Tumor necrosis factor α
- PBS:
-
Phosphate-buffered saline
- LPS:
-
Lipopolysaccharides
- LAM:
-
Lipoarabinomannan
References
Bartlett, J.A., A.J. Fischer, and P.B. McCray. 2008. Innate immune functions of the airway epithelium. Contributions to Microbiology 15: 147–163.
Hiemstra, P.S. 2007. The role of epithelial beta-defensins and cathelicidins in host defense of the lung. Experimental Lung Research 33: 537–542.
Laube, D.M., S. Yim, L.K. Ryan, K.O. Kisich, and G. Diamond. 2006. Antimicrobial peptides in the airway. Current Topics in Microbiology and Immunology 306: 153–182.
Lai, Y., and R.L. Gallo. 2009. MPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends in Immunology 30: 131–141.
Yang, D., Z.H. Liu, P. Tewary, Q. Chen, G. de la Rosa, and J.J. Oppenheim. 2007. Defensin participation in innate and adaptive immunity. Current Pharmaceutical Design 13: 3131–3139.
McCormick, T.S., and A. Weinberg. 2010. Epithelial cell-derived antimicrobial peptides are multifunctional agents that bridge innate and adaptive immunity. Periodontology 2000 54: 195–206.
Hollox, E.J., and J.A. Armour. 2008. Directional and balancing selection in human betadefensins. BMC Evolutionary Biology 8: 113.
Wehkamp, K., L. Schwichtenberg, J.M. Schröder, and J. Harder. 2006. Pseudomonas aeruginosa- and IL-1β-mediated induction of human beta-defensin-2 in keratinocytes is controlled by NF-kappaB and AP-1. Journal of Investigative Dermatology 126: 121–127.
Kao, C.Y., Y. Chen, P. Thai, S. Wachi, F. Huang, C. Kim, et al. 2004. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. Journal of Immunology 173: 3482–3491.
Yoon, Y.M., J.Y. Lee, D. Yoo, Y.S. Sim, Y.J. Kim, Y.K. Oh, et al. 2010. Bacteroides fragilis enterotoxin induces human beta-defensin-2 expression in intestinal epithelial cells via a mitogen-activated protein kinase/I kappaB kinase/NF-kappaB-dependent pathway. Infection and Immunity 78: 2024–2033.
Korn, T., E. Bettelli, M. Oukka, and V.K. Kuchroo. 2009. IL-17 and Th17 cells. Annual Review of Immunology 27: 485–517.
Aujla, S.J., and J.K. Kolls. 2009. IL-22: a critical mediator in mucosal host defense. Journal of Molecular Medicine 87: 451–454.
Aujla, S.J., Y.R. Chan, M. Zheng, M. Fei, D.J. Askew, D.A. Pociask, et al. 2008. IL-22 mediates mucosal host defense against gram-negative bacterial pneumonia. Nature Medicine 14: 275–281.
Kao, C.Y., C. Kim, F. Huang, and R. Wu. 2008. Requirements for two proximal NF-kappaB binding sites and IkappaB-zeta in IL-17A-induced human beta-defensin 2 expression by conducting airway epithelium. Journal of Biological Chemistry 283: 15309–15318.
Brand, S., F. Beigel, T. Olszak, K. Zitzmann, S.T. Eichhorst, J.M. Otte, et al. 2006. IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. American Journal of Physiology - Gastrointestinal and Liver Physiology 290: G827–G838.
Dumoutier, L., J. Louahed, and J.C. Renauld. 2000. Cloning and characterization of IL-10-related T cell derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. Journal of Immunology 164: 1814–1819.
Wolk, K., and R. Sabat. 2006. Interleukin-22: a novel T and NK cellderived cytokine that regulates the biology of tissue cells. Cytokine & Growth Factor Reviews 17: 367–380.
Wolk, K., S. Kunz, E. Witte, M. Friedrich, K. Asadullah, and R. Sabat. 2004. IL-22 increases the innate immunity of tissues. Immunity 21: 241–254.
Sugimoto, K., A. Ogawa, E. Mizoguchi, Y. Shimomura, A. Andoh, A.K. Bhan, et al. 2008. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. Journal of Clinical Investigation 118: 534–544.
Zheng, Y., P.A. Valdez, D.M. Danilenko, Y. Hu, S.M. Sa, Q. Gong, et al. 2008. Interleukin 22 mediates early host defense against attaching and effacing bacterial pathogens. Nature Medicine 14: 282–289.
Wolk, K., E. Witte, K. Warszawska, G. Schulze-Tanzil, K. Witte, S. Philipp, et al. 2009. The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. European Journal of Immunology 39: 3570–3581.
Ma, H.L., S. Liang, J. Li, L. Napierata, T. Brown, S. Benoit, et al. 2008. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. Journal of Clinical Investigation 118: 597–607.
Harder, J., U. Meyer-Hoffert, L.M. Teran, L. Schwichtenberg, J. Bartels, S. Maune, Mucoid, et al. 2000. Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. American Journal of Respiratory Cell and Molecular Biology 22: 714–721.
Mendez-Samperio, P., L. Alba, and A. Trejo. 2007. Mycobacterium bovismediated induction of human beta-defensin-2 in epithelial cells is controlled by intracellular calcium and p38MAPK. Journal of Infection 54: 469–474.
Rohrl, J., D. Yang, J.J. Oppenheim, and T. Hehlgans. 2010. Specific binding and chemotactic activity of mBD4 and its functional orthologue HBD2 to CCR6-expressing cells. Journal of Biological Chemistry 285: 7028–7034.
Zaiou, M. 2007. Multifunctional antimicrobial peptides: therapeutic targets in several human diseases. Journal of Molecular Medicine 85: 317–329.
Brogden, K.A. 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology 3: 238–250.
Cudic, M., and L. Otvos Jr. 2002. Intracellular targets of antibacterial peptides. Current Drug Targets 3: 101–106.
MacRedmond, R., C. Greene, C.C. Taggart, N. McElvaney, and S. O’Neill. 2005. Respiratory epithelial cells require Toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide. Respiratory Research 6: 116.
Romano Carratelli, C., N. Mazzola, R. Paolillo, S. Sorrentino, and A. Rizzo. 2009. Toll-like receptor-4 (TLR4) mediates human beta-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells. FEMS Immunology and Medical Microbiology 57: 116–124.
Donnarumma, G., I. Paoletti, E. Buommino, M.R. Iovene, L. Tudisco, V. Cozza, et al. 2007. Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line (A549) stimulated withlipopolysaccharide. Peptides 28: 2286–2292.
Acknowledgments
We thank the Department of Oncology of the First Affiliated Hospital of Nanjing Medical University for providing alveolar epithelial type II cell lines A549 and Cui Ping Liu for expert technical help.
Conflict of Interest
None of the authors of this study has any financial or commercial conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, A., Gan, Y., Wang, R. et al. IL-22 Up-Regulates β-Defensin-2 Expression in Human Alveolar Epithelium via STAT3 but Not NF-κB Signaling Pathway. Inflammation 38, 1191–1200 (2015). https://doi.org/10.1007/s10753-014-0083-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-014-0083-z