Stat3 Induces\nIL-10 and SR-A/CD204 Expression in Silica\nNanoparticle-Triggered Pulmonary Fibrosis through Transactivation

Inhalation of silica dust in the workplace has been addressed\nas\na serious occupational pulmonary disease subsequently leading to inflammation\nand fibrosis. Enhanced expression of IL-10 significantly contributes\nto the disease etiology, along with an elevated Th2-type paradigm.\nPreviously, we showed that the exaggerated Th2-type response was also\nassociated with consistent upregulation of Stat3 in mouse airways\nstimulated with silica microparticles. However, a precise understanding\nof silicosis in light of the IL-10/Stat3 immune axis is required.\nWe, therefore, aimed to determine the regulatory role of IL-10 in\nnanosized silica (nSiO<sub>2</sub>)-induced pulmonary fibrosis in\nassociation with Stat3. Herein, we report that amorphous nSiO<sub>2</sub> could induce pulmonary fibrosis with consistent and concomitant\nupregulation of IL-10, Stat3, and SR-A/CD204. Following exogenous\nadministration of siStat3 and rIL-10, the study further confirmed\nthat Stat3 mediates the regulation of IL-10 and SR-A/CD204 and that\nIL-10 could regulate its own expression in an autoregulatory loop.\nThe ChIP assay highlighted the localization of Stat3 over two putative\nbinding sites in the IL-10 promoter region, which subsequently resulted\nin the overexpression of SR-A/CD204. Conclusively, Stat3-mediated\ntransregulation of IL-10 through an autoregulatory loop in silicosis\ncould offer novel molecular targets for therapeutic interventions.