Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-alpha and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) enhanced TNF-alpha and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-kappa B was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-kappa B in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-alpha and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-kappa B/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne. (C) 2018 The Author(s) Published by S. Karger AG, Basel
[1]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Dermatol, Pujian Rd 160, Shanghai 200127, Peoples R China;
[2]Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, Shanghai, Peoples R China;
[3]Brandenburg Med Sch Theodore Fontane, Dessau Med Ctr, Dept Dermatol, Dessau, Germany;
[4]Brandenburg Med Sch Theodore Fontane, Dessau Med Ctr, Dept Venereol, Dessau, Germany;
[5]Brandenburg Med Sch Theodore Fontane, Dessau Med Ctr, Dept Allergol, Dessau, Germany;
[6]Brandenburg Med Sch Theodore Fontane, Dessau Med Ctr, Dept Immunol, Dessau, Germany;
[7]Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai, Peoples R China
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