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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1415350
This article is part of the Research Topic Unraveling the Molecular Mechanisms of Cytokine Signaling in Regulating Inflammatory Diseases View all 7 articles
Pregnane X receptor reduces particulate matter-induced type 17 inflammation in atopic dermatitis
Provisionally accepted- 1 Seoul National University Hospital, Seoul, Republic of Korea
- 2 College of Medicine, Seoul National University, Seoul, Seoul, Republic of Korea
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.
Keywords: Particulate Matter, Air Pollution, Pregnane X receptor, atopic dermatitis, type 17 inflammation
Received: 10 Apr 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Lee, Lee, Jang, Oh, Lee and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ji Su Lee, Seoul National University Hospital, Seoul, Republic of Korea
Youngae Lee, Seoul National University Hospital, Seoul, Republic of Korea
Sunhyae Jang, Seoul National University Hospital, Seoul, Republic of Korea
Dong Hun Lee, Seoul National University Hospital, Seoul, Republic of Korea
Soyun Cho, College of Medicine, Seoul National University, Seoul, 03080, Seoul, Republic of Korea
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