Overexpression of IFIT1 protects against LPS-induced acute lung injury via regulating CCL5-p65NF-κB signaling.

Int Immunopharmacol

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui Province, China; Department of Pharmacy, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China. Electronic address:

Published: January 2023

Acute lung injury (ALI) is featured by intensive inflammatory responses causing significant morbidity and mortality. Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), induced by interferon (IFN), has been discovered to modulate viral infection and cell apoptosis and inhibit the production of pro-inflammatory cytokines. However, it's role and mechanism in ALI remain unclear and need to be explored furtherly. Here, we discovered that IFIT1 decreased the expression of TNF-α, IL-1β and IL-6 in mouse-derived macrophage cells (MH-S) and alleviated apoptosis of murine lung epithelial cells (MLE-12) induced by MH-S cell supernatant, contributing to anti-inflammatory and antiapoptotic effects in vitro and in vivo. Moreover, RNA sequencing analysis (RNA-seq) showed that inflammatory chemokine CC motif chemokine ligand 5 (CCL5) partially eliminated the protective effects of IFIT1 and promoted the expression of inflammatory cytokines TNF-α, IL-1β and IL-6 by CCL5-p65NF-κB signaling pathway. This study demonstrated that IFIT1 attenuated ALI-associated inflammation and cell apoptosis by regulating the CCL5-p65NF-κB signaling pathway. These findings are of great significance for the treatment of lung injury.

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Source
http://dx.doi.org/10.1016/j.intimp.2022.109485DOI Listing

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