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

• Xuzhong Zhang ^[1] ; Wei Chen ^[1] ; Wei Liu ^[1] ; Donge Li ^[1] ; Wei Shen ^[1]
  1. [1] Department of Pediatric, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei City, Anhui Province, 230001, China
• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 50, Nº. 4, 2022, págs. 64-70
• Idioma: inglés
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• Resumen

  • 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 matu‑ration. 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 lipopolysac‑charides 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.