International immunopharmacology · 2024
Activation of aryl hydrocarbon receptor ameliorates degranulation of LL-37 induced mast cells in rosacea through enhancing autophagy.
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Chen Shuyan, Hu Honghao, Wu Jinxuan, Dong Miao, Zhang Ying, Zhu Qiao, Wang Zi, Sun Yan, Gao Xinghua
Аннотация
BACKGROUND: Activation of the aryl hydrocarbon receptor (AhR) ameliorates LL-37-induced rosacea-like dermatitis in mice, whereas mast cells and cytokine overexpression are prominent features in rosacea skin.
OBJECTIVE: To evaluate the potential mechanisms of AhR activation on autophagy and degranulation of mast cells in rosacea.
METHODS: LL-37 treated mast cells were used to mimic rosacea. An AhR agonist (tapinarof) was applied to LL-37 induced mast cells. Furthermore, an autophagy agonist (RAPA) and an inhibitor (CQ) was added to investigate the mechanisms of autophagy. Western blot and RT-qPCR assessed cell degranulation (Cma1, Tpsab1) and cytokines (MMP9, TNF-α, and IL-6). Changes in cell morphology were observed under a microscope. Autophagy markers (LC3 and p62) were examined using Western blot and cellular immunofluorescence.
RESULTS: LL-37 upregulated the expressions of Cma1, Tpsab1, MMP9, TNF-α, and IL-6, which were then reduced by tapinarof treatment for 24 h. LC3B-I was converted to LC3B-II and p62 was reduced gradually with increasing concentration of tapinarof, indicating that autophagy was enhanced. RAPA enhanced the expression of LC3B-II on LL-37-induced mast cells, similar to tapinarof, while CQ partially inhibited the ability of tapinarof to induce autophagy in mast cells. Moreover, CQ reversed tapinarof's suppression of Cma1, Tpsab1, MMP9, TNF-α and IL-6 on LL-37 treated mast cells.
CONCLUSION: The present study showed that activation of AhR ameliorated degranulation of LL-37-induced mast cells in rosacea through enhancing autophagy, offering a new option for rosacea treatment.
OBJECTIVE: To evaluate the potential mechanisms of AhR activation on autophagy and degranulation of mast cells in rosacea.
METHODS: LL-37 treated mast cells were used to mimic rosacea. An AhR agonist (tapinarof) was applied to LL-37 induced mast cells. Furthermore, an autophagy agonist (RAPA) and an inhibitor (CQ) was added to investigate the mechanisms of autophagy. Western blot and RT-qPCR assessed cell degranulation (Cma1, Tpsab1) and cytokines (MMP9, TNF-α, and IL-6). Changes in cell morphology were observed under a microscope. Autophagy markers (LC3 and p62) were examined using Western blot and cellular immunofluorescence.
RESULTS: LL-37 upregulated the expressions of Cma1, Tpsab1, MMP9, TNF-α, and IL-6, which were then reduced by tapinarof treatment for 24 h. LC3B-I was converted to LC3B-II and p62 was reduced gradually with increasing concentration of tapinarof, indicating that autophagy was enhanced. RAPA enhanced the expression of LC3B-II on LL-37-induced mast cells, similar to tapinarof, while CQ partially inhibited the ability of tapinarof to induce autophagy in mast cells. Moreover, CQ reversed tapinarof's suppression of Cma1, Tpsab1, MMP9, TNF-α and IL-6 on LL-37 treated mast cells.
CONCLUSION: The present study showed that activation of AhR ameliorated degranulation of LL-37-induced mast cells in rosacea through enhancing autophagy, offering a new option for rosacea treatment.