Interleukin-24: A molecular mediator of particulate matter’s impact on skin aging

• Published in: Ecotoxicology and environmental safety 2024-09, Vol.282, p.116738, Article 116738
• Main Authors: Seong, Seol Hwa, Kim, Ji Young, Kim, Sung Hee, Lee, Joohee, Lee, Eun Jung, Bae, Yu Jeong, Park, Sujin, Kwon, Il Joo, Yoon, Sei-Mee, Lee, Jinu, Kim, Tae-Gyun, Oh, Sang Ho
• Format: Article
• Language: English
• Subjects: Interleukin-24; Lovastatin; MMP1; Particulate matter; Skin aging
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116738

Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging. •IL-24 is upregulated in both keratinocytes and fibroblasts of PM-treated ex vivo skin.•PM-induced IL-24 spurs MMP1 secretion and collagen degradation akin to skin aging.•PM-induced IL-24 induces cellular senescence in human dermal fibroblasts.•High-throughput screening identified lovastatin as a potent IL-24-STAT3 inhibitor.•IL-24 plays an important role in PM-induced skin aging being a promising target.