Exp Mol Med.  2004 Jun;36(3):204-210.

Human beta-defensin 2 is induced by interleukin-1b in the cornealepithelial cells

• Shin JS
• Kim CW
• Kwon YS
• Kim JC

Abstract

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-kB 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-kB site activation, thus suggesting that the long distal portion of the promoter is needed for the full responsiveness toward IL-1beta.

Keyword

antimicrobial cationic peptides; beta-defensins; cornea; corneal epithelium; gene expression regulation; interleukin-1beta

MeSH Terms

Binding, Competitive
Cell Survival
Cells, Cultured
Corneal Diseases/metabolism
Electrophoretic Mobility Shift Assay
Epithelium, Corneal/drug effects/*immunology/metabolism
Gene Expression
Humans
Interferon Type II/metabolism/pharmacology
Interleukin-1/*pharmacology
Lipopolysaccharides/metabolism/pharmacology
NF-kappa B/metabolism
Promoter Regions (Genetics)/drug effects/genetics
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor-alpha/metabolism/pharmacology
beta-Defensins/*biosynthesis/genetics/metabolism