Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation.
Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy inhibition induced AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD- and chloroquine-induced p65NF-κB and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-κB/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis.
['Kim|Hye Ran|HR|0000-0001-7519-8910', 'Kang|Seok Young|SY|', 'Kim|Hye One|HO|', 'Park|Chun Wook|CW|', 'Chung|Bo Young|BY|']
D000818:Animals D001343:Autophagy D051792:Basic Helix-Loop-Helix Transcription Factors D002460:Cell Line D002478:Cells, Cultured D006801:Humans D007249:Inflammation D015603:Keratinocytes D011565:Psoriasis D018336:Receptors, Aryl Hydrocarbon D012867:Skin
aryl hydrocarbon receptor autophagy skin psoriasis 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)