Stat3 Induces IL-10 and SR-A/CD204 Expression in Silica Nanoparticle-Triggered Pulmonary Fibrosis through Transactivation.

ACS Biomater Sci Eng

Centre of Science and Society, Institute of Interdisciplinary Sciences (IIDS), University of Allahabad, Prayagraj 211002, India.

Published: December 2024

Inhalation of silica dust in the workplace has been addressed as a serious occupational pulmonary disease subsequently leading to inflammation and fibrosis. Enhanced expression of IL-10 significantly contributes to the disease etiology, along with an elevated Th2-type paradigm. Previously, we showed that the exaggerated Th2-type response was also associated with consistent upregulation of Stat3 in mouse airways stimulated with silica microparticles. However, a precise understanding of silicosis in light of the IL-10/Stat3 immune axis is required. We, therefore, aimed to determine the regulatory role of IL-10 in nanosized silica (nSiO)-induced pulmonary fibrosis in association with Stat3. Herein, we report that amorphous nSiO could induce pulmonary fibrosis with consistent and concomitant upregulation of IL-10, Stat3, and SR-A/CD204. Following exogenous administration of siStat3 and rIL-10, the study further confirmed that Stat3 mediates the regulation of IL-10 and SR-A/CD204 and that IL-10 could regulate its own expression in an autoregulatory loop. The ChIP assay highlighted the localization of Stat3 over two putative binding sites in the IL-10 promoter region, which subsequently resulted in the overexpression of SR-A/CD204. Conclusively, Stat3-mediated transregulation of IL-10 through an autoregulatory loop in silicosis could offer novel molecular targets for therapeutic interventions.

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http://dx.doi.org/10.1021/acsbiomaterials.4c01473DOI Listing

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