| First Author | Ge X | Year | 2019 |
| Journal | Cell Commun Signal | Volume | 17 |
| Issue | 1 | Pages | 18 |
| PubMed ID | 30813930 | Mgi Jnum | J:292463 |
| Mgi Id | MGI:6444990 | Doi | 10.1186/s12964-019-0331-9 |
| Citation | Ge X, et al. (2019) Vitamin D/VDR signaling inhibits LPS-induced IFNgamma and IL-1beta in Oral epithelia by regulating hypoxia-inducible factor-1alpha signaling pathway. Cell Commun Signal 17(1):18 |
| abstractText | BACKGROUND: Oral lichen planus (OLP) is known as a chronic inflammatory disease. Our recent studies have suggested that vitamin D/vitamin D receptor (VDR) signaling exerts its protective effects on oral keratinocyte apoptosis by regulating microRNA-802 and p53-upregulated modulator of apoptosis (PUMA), but its roles in oral epithelial inflammatory responses in OLP are still unknown. Herein, we identify lipopolysaccharide (LPS) is able to enhance interferon gamma (IFNgamma) and interleukin-1 beta (IL-1beta) productions in human oral keratinocytes (HOKs) dependent on hypoxia-inducible factor-1alpha (HIF-1alpha). METHODS: HIF-1alpha and cytokines levels in HOKs were investigated by real-time PCR and western blotting after LPS challenge. The effects of 1,25(OH)2D3 on LPS-induced HIF-1alpha and cytokines were tested by real-time PCR, western blotting, siRNA-interference and plasmids transfection techniques. The roles of 1,25(OH)2D3 in regulating HIF-1alpha levels were investigated using western blotting, siRNA-interference, plasmids transfection and Chromatin Immunoprecipitation (ChIP) assays. Finally, HIF-1alpha, IFNgamma and IL-1beta expressions in oral epithelia derived from mice and individuals were measured by real-time PCR, western blotting and immunohistochemical staining. RESULTS: As a critical regulator, vitamin D suppresses LPS-induced HIF-1alpha to block IFNgamma and IL-1beta productions. Mechanistically, vitamin D inactivates nuclear factor-kappaB (NF-kappaB) pathway and up-regulates von Hippel-Lindau (VHL) levels, leading to HIF-1alpha reduction. Moreover, HIF-1alpha status of oral epithelia is elevated in VDR(-/-) mie as well as in VDR-deficient human biopsies, accompanied with increased IFNgamma and IL-1beta. CONCLUSION: Collectively, this study uncovers an unrecognized roles of vitamin D/VDR signaling in regulating cytokines in oral keratinocytes and reveals the molecular basis of it. |
