Presenting Author: Youngheun Jee
, Professor at Jeju Natl. Univ. Col. of Vet. Med., Jeju Natl. Univ.
Abstract:
Particulate matter (PM) is increasingly recognized as a significant contributor to allergic inflammation in asthma. Recent studies have elucidated the exacerbation of airway inflammation in allergic asthmatic mice characterized by Th2/Th17 responses, primarily mediated via TLR4 and the MyD88-dependent NF-κB pathways. In this study, we investigated the role of TLR4 in PM-induced allergic asthma by comparing pathogenesis and immunology in TLR4+/+ and TLR4-/- mice. TLR4+/+ mice showed a marked macrophage polarization disparity: PM exposure increased CD80+ M1 macrophages, while OVA exposure elevated CD206+ M2 macrophages. Additionally, PM exposure in OVA-induced TLR4-/- mice markedly amplified oxidative DNA damage in both M1 and M2 macrophages. Concurrently, mRNA expression of TLR4, Th17 transcription factor RORγt, and cytokines IL-17A, IL-22, TGF-β was all promoted as implicated in airway inflammation upon PM exposure. Intriguingly, the secretion of cytokines by M1 (IL-1β, TNF-α, IL-6) and M2 (IL-4, IL-10) macrophages, as well as the inflammatory cytokines by Th17 cells was reduced in the splenocytes of TLR4-/- mice. Histological examination of lung tissues from TLR4-/- mice showed reduced inflammatory cell infiltration, mucus hypersecretion, and mast cell activation compared to TLR4+/+ mice. These results suggest that TLR4 plays a crucial role in the development of asthma upon PM exposure by modulating M1/M2 macrophage polarization and Th17 cell cytokine production.