Cdk2 suppresses IL‐23 expression and the onset of severe acute pancreatitis. Issue 6 (19th May 2022)

• Record Type: Journal Article
• Authors: Ma, Yanpeng; Liu, Longlong; Li, Bin; Wang, Wenyao; Zhao, Tingting
• Is Part Of: Immunity, inflammation and disease. Volume 10:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-19
• Subjects: acute pancreatitis -- CDK -- DCAF2 -- IL‐23 -- macrophages; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.631
• Languages: English
• ISSNs: 2050-4527

Abstract

Abstract: Background: Acute pancreatitis is a sudden inflammation of the pancreas. Although interleukin‐23 (IL‐23) is associated with the severity of acute pancreatitis, the underlying mechanism remains largely unknown. Herein, its regulatory mechanisms were explored in this study. Methods: RNA‐sequencing analysis selected the differently expressed genes in cerulean‐induced acute pancreatitis mice. Polymerase chain reaction analysis determined IL‐23 expression in cyclin‐dependent kinase 2 (Cdk2) short hairpin RNA (shRNA)‐pretreated or DDB1–cullin‐4‐associated factor‐2 (DCAF2)‐overexpressed RAW264.7 cells or CDKs inhibitor AT7519/cullin ring‐finger ubiquitin ligase inhibitor MLN4924‐treated bone marrow‐derived macrophages in the presence of lipopolysaccharides (LPS). Pancreatic damages were evaluated in AT7519‐treated pancreatitis mice. Results: Pancreatitis mice displayed an increased expression on IL‐23 and a decreased expression of Cdk2. Inhibiting Cdk2 by shRNA or AT7519 significantly induced IL‐23 expression in LPS‐treated RAW cells. Moreover, AT7519 treatment significantly aggravated the severity of acute pancreatitis in mice. Furthermore, AT7519 remarkably increased DCAF2 expression, which was also induced by MLN4924 no matter with or without AT7519 in vitro. On the contrary, overexpressing DCAF2 blocked the stimulatory effect of AT7519 on IL‐23 expression. Conclusion: Cdk2 negatively regulates IL‐23 expression by inhibiting DCAF2 in acute pancreatitis, indicating that Cdk2 might serve as a promising therapeutic target for acute pancreatitis. Abstract : Cyclin‐dependent kinases (CDKs) inhibitor AT7519 aggravated acute pancreatitis in mice. CDKs inhibitor AT7519 suppressed interleukin‐23 (IL‐23) expression by regulating DDB1–cullin‐4‐associated factor‐2 expression.