Deficiency of Toll-like receptor 4 attenuates airway inflammation and remodeling in an ovalbumine-induced mouse asthma model.

Previous research has demonstrated elevated levels of Toll-like receptor 4 (TLR4) in the lung tissues of asthmatic mice compared to healthy counterparts, with a notable association between asthmatic inflammation and the sustained activation of the nuclear factor kappa-B (NF-κB) pathway. The specific role of TLR4 in modulating airway inflammation and remodeling, however, remains unclear. This study aimed to explore the impact of TLR4 deficiency on airway inflammation and remodeling in an ovalbumin (OVA)-induced mouse asthma model and to elucidate the underlying mechanisms involved. To induce murine airway remodeling, an acute OVA sensitization and challenge protocol was employed. Pathological alterations in the lung tissues were assessed using hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome staining. Our findings indicated that there were significant reductions in inflammatory cell infiltration in TLR4 knockout (KO) mice, including eosinophils, lymphocytes, neutrophils and the levels of Th2 cytokines interleukin-4, 5, 13 (IL-4, IL-5, IL-13), while showing increased expression of Th1 cytokines [interferon-gamma (IFN-γ)] and a higher T-bet/GATA-3 ratio. Furthermore, TLR4 deficiency markedly decreased airway mucous production, collagen deposition and airway smooth muscle thickness, all of which are strongly associated with airway remodeling. Additionally, TLR4 KO enhanced inhibitor of NF-κB (IκB) protein expression in lung tissues, suggesting an inhibition of the TLR4/NF-κB pathway. These results demonstrate that TLR4 deficiency attenuates airway inflammation and remodeling, potentially through the inhibition of the TLR4/NF-κB signaling pathway in an OVA-induced mouse asthma model.