ArticleFrontiers in toxicology2026
Role of the protease-activated receptor 2 in multi-walled carbon nanotube-induced macrophage polarization
Article in Frontiers in toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Our previous work demonstrated that co-exposure to multi-walled carbon nanotubes (MWCNTs) exacerbates allergic lung disease induced by house dust mite (HDM) extract, and that mice deficient in protease-activated receptor 2 (PAR2) show less airway fibrosis following co-exposure. In this study, we examined the role of PAR2 in mediating macrophage polarization in the presence of MWCNTs under Th2-like conditions and the subsequent effects on fibroblast activation Methods: Bone marrow-derived macrophages (BMDMs), murine Results: MWCNTs exacerbated IL-4/IL-13-induced M2 polarization, increasing Arg-1 and phosphorylated STAT6 levels in both BMDMs and mexAMs. This enhancement was attenuated in PAR2-deficient macrophages. Conditioned media from M2-polarized WT macrophages induced significantly higher expression of profibrotic genes, including Conclusion: MWCNT exposure exacerbates Th2-driven M2 macrophage polarization in a PAR2-dependent manner, leading to increased fibroblast activation and collagen deposition. Myeloid PAR2 is a critical driver of fibrotic remodeling in allergic lung disease, representing a potential therapeutic target for mitigating fibrosis in environmentally exacerbated asthma.
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