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

Area of Science:

• Environmental Health
• Dermatology
• Immunology

Background:

• Epidemiological studies link particulate matter (PM) exposure to atopic dermatitis (AD) exacerbation.
• The precise mechanisms driving PM-induced AD remain unclear.
• Pregnane X receptor (PXR) has emerged as a potential factor in skin inflammation associated with AD.

Purpose of the Study:

• To investigate the impact of PM exposure on AD.
• To elucidate the role of PXR in PM-induced AD pathogenesis.

Main Methods:

• Utilized in vivo and in vitro AD-like models, including BALB/c mice, HaCaT cells, and mouse CD4 T cells.
• Assessed dermatitis scores, skin thickness, and inflammatory mediator levels (IL-17A, IL-23A, IL-1β, IL-6).
• Examined PXR signaling pathways, including PXR knockdown and activation with rifampicin, and its effect on the NF-κB pathway.

Main Results:

• PM exposure significantly worsened dermatitis and skin thickness in AD models.
• PM increased type 17 inflammatory mediators in both mouse and human skin cells.
• PXR activation by rifampicin reduced PM-induced inflammation, while PXR knockdown exacerbated it.
• PXR activation was found to inhibit the NF-κB signaling pathway.

Conclusions:

• PM exposure triggers type 17 inflammation and PXR activation in AD.
• PXR activation ameliorates PM-induced type 17 inflammation by suppressing the NF-κB pathway.
• PXR is a potential therapeutic target for managing PM-aggravated AD.