CITED2 alleviates lipopolysaccharide-induced inflammation and pyroptosis in - human lung fibroblast by inhibition of NF-κB pathway

Main Article Content

Xuzhong Zhang
Wei Chen
Wei Liu
Donge Li
Wei Shen

Keywords

CITED2, lipopolysaccharide, human lung fibroblasts, inflammation, pyroptosis, NF-κB

Abstract

Background: Pneumonia, a severe infectious respiratory disease, is one of the leading causes of mortality and morbidity in children. Cbp/P300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) functions as a transcription cofactor, and plays critical roles in the development of embryonic and extra-embryonic tissues, including fetal lung maturation. The present study investigates the role of CITED2 in infantile pneumonia.


Methods: The human fetal lung fibroblasts (MRC-5 and WI-38) were treated with lipopolysaccharides to induce cytotoxicity, and the cell viability was detected by MTT. Inflammation was evaluated by ELISA, and western blot was used to investigate the pyroptosis.


Results: CITED2 was down-regulated in lipopolysaccharide-treated MRC-5/WI-38 cells. The over-expression of CITED2 protected MRC-5 and WI-38 cells from lipopolysaccharide--induced cytotoxicity by increasing the cell viability and decreasing LDH expression. CITED2 reduced the expression of TNF-α, IL-6, IL-1β in lipopolysaccharide-treated MRC-5/WI-38 cells. Lipopolysaccharide stimulated pyroptosis in MRC-5 and WI-38 cells through the up-regulation of NL+RP3, GSDMD-N, caspase-1, IL-1β and IL-18. However, CITED2 down-regulated the expression of NLRP3, GSDMD-N, caspase-1, IL-1β, and IL-18 protein in lipopolysaccharide-treated MRC-5/WI-38 cells. CITED2 also down-regulated the protein expression of p-p65 in lipopolysaccharide--treated MRC-5/WI-38 cells.


Conclusion: CITED2 exhibited anti-inflammatory effect on lipopolysaccharide-treated human lung fibroblasts and reduced pyroptosis through inactivation of NF-κB pathway.

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