Pregnane X receptor reduces particulate matter-induced type 17 inflammation in atopic dermatitis.

Autor:	Lee JS; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea., Lee Y; Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea.; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea., Jang S; Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea.; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea., Oh JH; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea., Lee DH; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea.; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea., Cho S; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.; Department of Dermatology, Seoul Metropolitan Government - Seoul National University (SMG-SNU) Boramae Medical Center, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 27; Vol. 15, pp. 1415350. Date of Electronic Publication: 2024 Sep 27 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1415350
Abstrakt:	Background: Epidemiological evidence suggests that particulate matter (PM) exposure can trigger or worsen atopic dermatitis (AD); however, the underlying mechanisms remain unclear. Recently, pregnane X receptor (PXR), a xenobiotic receptor, was reported to be related to skin inflammation in AD. Objectives: This study aimed to explore the effects of PM on AD and investigate the role of PXR in PM-exposed AD. Methods: In vivo and in vitro AD-like models were employed, using BALB/c mice, immortalized human keratinocytes (HaCaT), and mouse CD4 + T cells. Results: Topical application of PM significantly increased dermatitis score and skin thickness in AD-like mice. PM treatment increased the mRNA and protein levels of type 17 inflammatory mediators, including interleukin (IL)-17A, IL-23A, IL-1β, and IL-6, in AD-like mice and human keratinocytes. PM also activated PXR signaling, and PXR knockdown exacerbated PM-induced type 17 inflammation in human keratinocytes and mouse CD4 + T cells. In contrast, PXR activation by rifampicin (a human PXR agonist) reduced PM-induced type 17 inflammation. Mechanistically, PXR activation led to a pronounced inhibition of the nuclear factor kappa B (NF-κB) pathway. Conclusion: In summary, PM exposure induces type 17 inflammation and PXR activation in AD. PXR activation reduces PM-induced type 17 inflammation by suppressing the NF-κB signaling pathway. Thus, PXR represents a promising therapeutic target for controlling the PM-induced AD aggravation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Lee, Lee, Jang, Oh, Lee and Cho.)
Databáze:	MEDLINE
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