Mechanisms of concanavalin A-induced cytokine synthesis by hepatic stellate cells: Distinct roles of interferon regulatory factor-1 in liver injury.

ABSTRACT: Mice depleted of hepatic stellate cells (HSCs) are protected from concanavalin A (ConA)-induced liver injury that is mediated by the activation of interferon regulatory factor 1 (IRF1). The aim of this study was to determine the mechanisms of ConA-mediated signaling and synthesis/release of mediators by HSCs that damage hepatocytes. Primary cultures of wildtype (WT) and IRF1-knockout (KO) HSCs and hepatocytes were used, and ConA-induced liver damage in interferon (IFN)αβ receptor-deficient (IFNαβR-KO) mice was determined. Specific binding of ConA to HSCs induced rapid activation of JAK2 and STAT1. ConA-induced expression of IRF1, IFNβ, tumor necrosis factor α, and CXCL1 was abrogated by selective inhibition of JAK2 and STAT1. Despite activating JAK2/STAT1, ConA failed to stimulate expressi

SUBMITTER: Rani R 

PROVIDER: S-EPMC6290141 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature