The Role And Mechanism Of Aryl Hydrocarbon Receptor-TLR2 Pathway In The Pathogenesis Of Acne

Background: Acne is a chronic inflammatory skin disease of hair follicle sebaceous glands,the mechanism of inducing and aggravating by environmental pollution or is unknown.In this study,we observed the effects of environmental pollutants benzopyrene,dioxin(TCDD),peptidoglycan(PGN)and Propionibacterium acnes on the expression of inflammatory cytokines in SZ95 human sebocytes and the activation of innate immunity pathway.And to observe the effect of P.acnes on the AhR pathway in skin follicles by in vitro cultured live skin model to explore the mechanism of aggravating acne induced by the environmental pollution.It was also found that resveratrol,an aryl hydrocarbon receptor(AhR)inhibitor,reduced the expression of cytokines induced by PGN and P.acnes and inhibited the innate immune pathways.Methods: The expressions of inflammatory cytokines in sebocytes of SZ95 cells stimulated by benzopyrene,TCDD,PGN and P.acnes were detected by RT-PCR and ELISA.The expressions of proteins in innate immunity and AhR signaling pathways induced by P.acnes,TCDD and PGN were detected by Western-blot,immunohistochemistry and immunofluorescence staining.Results: P.acnes can significantly stimulate the production of IL-1α,IL-1β and TNF-α in human sebocytes.PGN can significantly stimulate the production of IL-1α,IL-8 and TNF-α in human sebocytes.Inhibition or silencing of AhR can reduce cytokines produced by PGN and P.acnes,inhibit PGN-induced phosphorylation of p38 MAPK(mitogen-activated protein kinase)and p65 NF-κB(nuclear factor-κB).And TCDD can enhance PGN-induced IL-8 and TNF-α secretion,My D88 expression and phosphorylation of p38MAPK(mitogen activated protein kinase)and p65 NF-κB(nuclear factor-κB).P.acnes and PGN can activate AhR to induce the increase of CYP1A1 expression.Resveratrol can inhibit the expression of CYP1A1 and My D88 and the expression of cytokines induced by PGN and P.acnes.Conclusions: Environmental pollutants benzopyrene and TCDD can enhance the expression of inflammatory cytokines and activation of innate immune signaling pathways stimulated by PGN and P.acnes.AhR silencing can block this enhancement effect,indicating that this effect is AhR-dependent,which may be one of the mechanisms that environmental pollution induces and aggravate acne.In the meantime,PGN and P.acnes activate aryl hydrocarbon receptor to induce CYP1A1 expression,which may affect the proliferation and differentiation of sebocyte.