Hou Lixia, Song Sijia, Xiao Bo, Li Zhimei, Zhang Bingxi, Feng Xinru, Mo Biwen, Yao Dong
Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, China.
J Thorac Dis. 2025 Mar 31;17(3):1491-1501. doi: 10.21037/jtd-24-1751. Epub 2025 Mar 12.
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.
先前的研究表明，与健康小鼠相比，哮喘小鼠肺组织中Toll样受体4（TLR4）水平升高，且哮喘炎症与核因子κB（NF-κB）通路的持续激活之间存在显著关联。然而，TLR4在调节气道炎症和重塑中的具体作用仍不清楚。本研究旨在探讨TLR4缺陷对卵清蛋白（OVA）诱导的小鼠哮喘模型中气道炎症和重塑的影响，并阐明其潜在机制。
采用急性OVA致敏和激发方案诱导小鼠气道重塑。使用苏木精和伊红、过碘酸希夫和Masson三色染色评估肺组织的病理改变。
我们的研究结果表明，TLR4基因敲除（KO）小鼠的炎症细胞浸润显著减少，包括嗜酸性粒细胞、淋巴细胞、中性粒细胞以及Th2细胞因子白细胞介素-4、5、13（IL-4、IL-5、IL-13）的水平，同时Th1细胞因子[干扰素-γ（IFN-γ）]的表达增加，T-bet/GATA-3比值升高。此外，TLR4缺陷显著降低气道黏液分泌、胶原沉积和气道平滑肌厚度，所有这些都与气道重塑密切相关。此外，TLR4基因敲除增强了肺组织中NF-κB抑制蛋白（IκB）的表达，表明对TLR4/NF-κB通路有抑制作用。
这些结果表明，在OVA诱导的小鼠哮喘模型中，TLR4缺陷可能通过抑制TLR4/NF-κB信号通路减轻气道炎症和重塑。
