No abstract

Vitamin D is known to play a protective role in inflammatory diseases. Although the suppressive effect of vitamin D/vitamin D receptor (VDR) signaling has been shown in the context of oral lichen planus (OLP), the molecular basis of its regulatory function remains poorly understood. Herein, we reported that miR-802 overexpression in OLP could aggravate apoptosis of oral keratinocytes by targeting B-cell lymphoma 2 mRNA. In addition, vitamin D/VDR signaling was able to suppress miR-802 expression in LPS-treated or activated CD4 T cell-stimulated human oral keratinocytes by blocking NF-κB pathways, thereby inhibiting OLP apoptosis. Consistent with the results in vitro, we showed that miR-802 expression was enhanced in oral keratinocytes from VDR mice, and an inverse correlation between VDR and miR-802 was found in human biopsy specimens of OLP. Collectively, our data suggest that vitamin D/VDR signaling suppresses oral keratinocyte apoptosis by targeting miR-802.-Zhao, B., Xu, N., Li, R., Yu, F., Zhang, F., Yang, F., Ge, X., Li, Y. C., Du, J. Vitamin D/VDR signaling suppresses microRNA-802-induced apoptosis of keratinocytes in oral lichen planus.

These results suggest that 1,25(OH) D plays an anti-inflammatory role in OLP by mediating NF-κB signaling pathway but not AP-1 signaling pathway with a VDR-dependent manner, predicting vitamin D supplement may be a potential strategy for the OLP management.

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) 2 D 3 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) 2 D 3 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.

No abstract

The suppressive function of vitamin D on oral lichen planus (OLP) have been documented previously. Vitamin D receptor (VDR) expression is down-regulated in OLP, but the molecular mechanism of its decrease and the related anti-inflammatory contributor of epithelial VDR signaling is unclear. Herein, we demonstrated that lipopolysaccharide (LPS) remarkedly down-regulated VDR expression of keratinocytes, and the reduced regulation was dependent on tumor necrosis factor alpha (TNFα)-miR-346 pathway. In human specimen studies, VDR levels of oral mucosal epithelia from OLP patients decreased substantially accompanied with robust TNFα and miR-346 induction, compared to the normal tissues. In addition, vitamin D/VDR signaling inhibited LPS-induced p53-upregulated modulator of apoptosis (PUMA) induction in keratinocytes via impeding nuclear factor-κB (NF-κB) activation, resulting in keratinocytes apoptosis reduction. Importantly, PUMA activity was up-regulated strongly in diseased epithelium, reversely correlated with VDR expression. Totally, our data indicate that LPS is responsible for VDR downregulation in oral keratinocytes, which is associated with OLP development.

A photoredox-catalyzed sulfonylation of silyl enol ethers with DABCO•(SO 2 ) 2 and thianthrenium salts is achieved, providing diverse β-keto sulfones in moderate to good yields. This protocol features easily accessible starting materials and good functional group compatibility, enabling the introduction of various functionalized sulfonyl groups into ketones. Furthermore, as one of the important industrial raw materials, methanol can be employed as the methyl source to prepare α-methylsulfonated ketones through a methyl thianthrenium intermediate for the first time.

By employing CuOAc as the catalyst, we realize a four-component reaction of 1,3-enynes, diselenides, DABCO·(SO2)2, and cycloketone oxime esters, providing facile access to diverse cyanoalkylsulfonylated allenyl selenides in moderate to good yields. This reaction features high functional group tolerance and a broad substrate scope, enabling the regioselective, sequential formation of C–SO2 and C–Se bonds under mild reaction conditions. Moreover, the utility of this methodology is further illustrated through the late-stage functionalization of drug-based molecules.