Human beta-defensin 2 is induced by interleukin-1beta in the corneal epithelial cells.
Mammalian epithelia produce the various antimicrobial peptides against the bacterial or viral infection, thereby acting as the active immune modulators in the innate immunity. In this study, we examined the effects of the various proinflammatory cytokines or LPS on cell viability and antimicrobial beta-defensin gene expressions in human corneal epithelial cells. Results showed that the cytokines or LPS did not exert severe cytotoxic effects on the cells, and that beta-defensin 1 was constitutively expressed, while beta-defensin 2 was specifically induced by IL-1beta, supporting the idea that these cytokines or LPS involve the defense mechanism in the cornea. Furthermore, the reporter and gel shift assay to define the induction mechanism of beta-defensin 2 by IL-1beta demonstrated that the most proximal NF-kappaB site on the promoter region of beta-defensin 2 was not critical for the process. Data obtained from the normal or patients with the varying ocular diseases showed that our in vitro results were relevant in the clinical settings. Our results clearly demonstrated that beta-defensin 1 and 2 are important antimicrobial peptides in the corneal tissues, and that the mechanistic induction process of beta-defensin 2 by IL-1beta is not solely dependent on proximal NF-kappaB site activation, thus suggesting that the long distal portion of the promoter is needed for the full responsiveness toward IL-1beta.
Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Jun-Seop
JS
Shin
Chan-Wha
CW
Kim
Young-Sam
YS
Kwon
Jae-Chan
JC
Kim
D001667:Binding, Competitive; D002470:Cell Survival; D002478:Cells, Cultured; D003316:Corneal Diseases / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D019573:Epithelium, Corneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D007371:Interferon-gamma