Resveratrol represses tumor necrosis factor /c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells.
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OBJECTIVES: To study the effects of polyphenol resveratrol on TNF-induced inflammatory signaling as well as the underlying mechanism in human dental pulp stem cells (DPSCs). MATERIALS AND METHODS: Human DPSCs were cultured and treated by TNF in the presence or absence of resveratrol. NF-B and mitogen-activated protein kinase (MAPK) signaling pathways were analyzed by Western blotting and immunofluorescence staining. Interleukin 6 (IL6) and interleukin 8 (IL8) mRNA levels were analyzed by reverse transcription polymerase chain reaction. For the mechanistic study, autophagy was examined and further manipulated by gene silencing of Atg5 using siRNAs. Statistical analysis was performed by Student's t- test, and values of p<0.05 were considered significant. RESULTS: Upon TNF treatments, neither degradation of IB nor the phosphorylation and nuclear translocation of p65 NF-B were inhibited by resveratrol at different concentrations. In contrast, resveratrol dramatically inhibited TNF-induced phosphorylation of c-Jun N-terminal kinase (JNK) MAPK. Furthermore, resveratrol activated autophagy, as evidenced by the accumulated autophagic puncta formed by lipid bound LC3B in resveratrol-treated cells. Intriguingly, both resveratrol and JNK inhibitor SP600125 suppressed TNF-induced IL6 and IL8 mRNA expression (P<0.05). Silencing autophagy gene Atg5 led to the hyper-activation of JNK and augmented TNF-induced IL6 and IL8 mRNA expression (P<0.05). CONCLUSIONS: The results suggest that resveratrol suppresses TNF-induced inflammatory cytokines expressed by DPSCs through regulating the inhibitory autophagy-JNK signaling cascade. Resveratrol might be beneficial to ameliorate pulpal damage during the acute phase of inflammation in vital pulp therapy.