抄録
Defensins constitute a family of cationic antimicrobial peptides found in various animals, and act as key elements in the innate host defense. Mammalian defensins are deviled into α- and β-defensin subfamilies. In human, β-defensins (hBDs) are expressed in many epithelial tissues including trachea, skin, and intestine. Interestingly, expression of hBD1 is constitutive, while hBD2 expression is strongly induced in response to bacteria infection and proinflammatory cytokines. The promoter region of hBD2 gene contains several consensus binding sites for NFκB (nuclear factor κB), C/EBPβ (CCAAT/enhancer-binding protein β) and IFN-γ, suggesting inflammatory signaling may elicit the induction of hBD2 expression. However, the regulation mechanism of hBD expressions is little known.
To clarify the transcriptional regulation of hBD genes, we investigated their promoter activities in response to LPS using CD 14+ macrophage-like RAW 264.7 cells. The hBD1 promoter was not responsible to LPS, although the region from -162 to -70 was essential for its constitutive transcription. In contrast, the transcriptional activity of hBD2 promoter, which contained 3 potent NFκB binding sites at -2270, -576, and -208, was increased in response to LPS. Mutation or deletion of the NFκB site at -576 caused a 90% decrease in LPS response. Furthermore, gel mobility shift assay indicated that LPS increased NFκB binding activity with the -576 site on the hBD2 promoter. These observations suggest that the interaction between NFκB and the -576 site is important for LPS response of hBD2 promoter. Macrophages and epithelial cells express Toll-like receptors (TLRs) which induce activation of NFκB. Taken together, the TLR-NFκB pathway is likely involved in the LPS-induced transcription of hBD2 gene.
