Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells

Zhang,Yuntao; Zhang,Wang

doi:10.3892/mmr.2020.11109

Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells

Authors:
- Yuntao Zhang
- Wang Zhang
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Affiliations: Department of Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: May 4, 2020 https://doi.org/10.3892/mmr.2020.11109
Pages: 534-542
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary epithelial barrier dysfunction is a critical pathological component of lung injury, caused primarily by impaired epithelial cell migration. Moreover, macrophage‑epithelial interactions in pulmonary alveoli may either protect or damage epithelial barrier function. To investigate the effects of different macrophage subtypes, M1 and M2, on lipopolysaccharide (LPS)‑induced epithelial barrier dysfunction, M1 and M2 macrophages were used to treat LPS‑injured musculus lung epithelial cells (MLE‑12). Barrier function was evaluated by monitoring cell monolayer permeability, T‑cell immunoglobulin mucin 3 (Tim‑3) small interfering RNA and anti‑mouse Tim‑3 antibody were used to knockdown or block endogenous Tim‑3, to verify the role of the Tim‑3 in macrophage‑mediated barrier protection in LPS‑injured MLE‑12 cells. LY294002 was used to inhibit the activity of PI3K to verify the role of the PI3K/Akt signaling pathway in the restoration of epithelial cell. The present results revealed that co‑culture of LPS‑treated epithelial MLE‑12 cells with M1 macrophages decreased cell migration and promoted permeability, whereas co‑culture with M2 macrophages caused the opposite effects. It was determined that blocking T‑cell immunoglobulin mucin 3 (Tim‑3) signaling in macrophages and PI3K/Akt signaling in epithelial cells eliminated the barrier protection supplied by M2 macrophages. Tim‑3, which maintains macrophage M2 polarization, is a key component of the macrophage‑mediated barrier‑repair process, while M2 macrophages regulate PI3K/Akt signaling in epithelial cells, which in turn enhances pulmonary epithelial barrier function by restoring cell migration.

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