Vitamin D/VDR signaling inhibits LPS-induced IFNγ and IL-1β in Oral epithelia by regulating hypoxia-inducible factor-1α signaling pathway
| Autor: | Ran Li, Feiyan Yu, Jie Du, Mengdi Li, Fang Zhang, Fang Yang, Lixiang Wang, Xuejun Ge, Bin Zhao, Na Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
Lipopolysaccharides Male Interleukin-1beta HIF-1α lcsh:Medicine Biochemistry Calcitriol receptor Epithelium Cell Line Interferon-gamma Calcitriol Vitamin D and neurology medicine Animals Humans Interferon gamma Vitamin D lcsh:QH573-671 Molecular Biology Mouth Base Sequence Chemistry lcsh:Cytology Research lcsh:R NF-kappa B Cell Biology Transfection Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Up-Regulation Mice Inbred C57BL Blot Hypoxia-inducible factors Von Hippel-Lindau Tumor Suppressor Protein Apoptosis Vitamin D receptor Oral lichen planus Receptors Calcitriol Cytokines Signal transduction Lichen Planus Oral Signal Transduction medicine.drug |
| Zdroj: | Cell Communication and Signaling, Vol 17, Iss 1, Pp 1-10 (2019) Cell Communication and Signaling : CCS |
| Popis: | 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 (IFNγ) and interleukin-1 beta (IL-1β) productions in human oral keratinocytes (HOKs) dependent on hypoxia-inducible factor-1α (HIF-1α). Methods HIF-1α 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-1α 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-1α levels were investigated using western blotting, siRNA-interference, plasmids transfection and Chromatin Immunoprecipitation (ChIP) assays. Finally, HIF-1α, IFNγ and IL-1β 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-1α to block IFNγ and IL-1β productions. Mechanistically, vitamin D inactivates nuclear factor-κB (NF-κB) pathway and up-regulates von Hippel-Lindau (VHL) levels, leading to HIF-1α reduction. Moreover, HIF-1α status of oral epithelia is elevated in VDR−/− mie as well as in VDR-deficient human biopsies, accompanied with increased IFNγ and IL-1β. 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. Electronic supplementary material The online version of this article (10.1186/s12964-019-0331-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |