Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Oklahoma City, OK, 73117, USA.
Inflammation. 2022 Dec;45(6):2142-2162. doi: 10.1007/s10753-022-01708-y. Epub 2022 Jul 2.
Lung epithelium is constantly exposed to the environment and is critically important for the orchestration of initial responses to infectious organisms, toxins, and allergic stimuli, and maintenance of normal gaseous exchange and pulmonary function. The integrity of lung epithelium, fluid balance, and transport of molecules is dictated by the tight junctions (TJs). The TJs are formed between adjacent cells. We have focused on the topic of the TJ structure and function in lung epithelial cells. This review includes a summary of the last twenty years of literature reports published on the disrupted TJs and epithelial barrier in various lung conditions and expression and regulation of specific TJ proteins against pathogenic stimuli. We discuss the molecular signaling and crosstalk among signaling pathways that control the TJ structure and function. The Toll-like receptor-4 (TLR4) recognizes the pathogen- and damage-associated molecular patterns released during lung injury and inflammation and coordinates cellular responses. The molecular aspects of TLR4 signaling in the context of TJs or the epithelial barrier are not fully known. We describe the current knowledge and possible networking of the TLR4-signaling with cellular and molecular mechanisms of TJs, lung epithelial barrier function, and resistance to treatment strategies.
肺上皮细胞不断暴露于环境中，对于协调对感染源、毒素和过敏刺激的初始反应以及维持正常气体交换和肺功能至关重要。肺上皮细胞的完整性、液体平衡和分子转运由紧密连接（TJ）决定。TJ 形成于相邻细胞之间。我们专注于肺上皮细胞中 TJ 结构和功能的主题。这篇综述包括过去二十年关于各种肺部疾病中 TJ 破坏和上皮屏障以及针对致病刺激的特定 TJ 蛋白表达和调节的文献报告的总结。我们讨论了控制 TJ 结构和功能的信号通路之间的分子信号和串扰。Toll 样受体-4（TLR4）识别在肺损伤和炎症期间释放的病原体和损伤相关的分子模式，并协调细胞反应。TLR4 信号在 TJ 或上皮屏障中的分子方面尚不完全清楚。我们描述了 TLR4 信号与 TJ、肺上皮屏障功能和对治疗策略的抵抗力的细胞和分子机制的现有知识和可能的网络。
