Pyk2 inhibitor prevents epithelial hyperpermeability induced by HMGB1 and inflammatory cytokines in Caco-2 cells.

ABSTRACT: The non-receptor protein tyrosine kinase 2β (Pyk2) phosphorylated tricellular tight junction (tTJ) molecules angulin-1/LSR and tricellulin (TRIC) and the inhibitor PF-431396 (PF43) suppress angulin-1/LSR and TRIC recruitment to tTJs. The disruption of the intestinal epithelial barrier by high mobility group box 1 (HMGB1) and the inflammatory cytokines TNFα and IFNγ contributes to downregulation of angulin-1/LSR and TRIC in 2.5D culture of Caco-2 cells as a novel model of inflammatory bowel disease (IBD). In the present study, to investigate the roles of Pyk2 phosphorylated angulin-1/LSR and TRIC in the intestinal epithelial barrier, 2D and 2.5D cultures of Caco-2 cells were treated with the Pyk2 inhibitor PF-43 with or without HMGB1, inflammatory cytokines TNFα and IFNγ. Treatment with PF-

SUBMITTER: Konno T 

PROVIDER: S-EPMC8078543 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature