Intestinal epithelial chemokine (C-C motif) ligand 7 overexpression enhances acetaminophen-induced hepatotoxicity in mice.

Intestinal epithelial chemokine (C-C motif) ligand 7 overexpression enhances acetaminophen-induced hepatotoxicity in mice. Am J Pathol. 2019 Oct 11;: Authors: Niu M, Luo Z, Gong S, Win S, Kaplowitz N, Jiang Y, Chen P Abstract Acetaminophen (APAP) overdose-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. The related injury pathogenesis is mainly focused on the liver. Here, we report that gut barrier disruption may also be involved in APAP hepatotoxicity. APAP administration led to gut leakiness and colonic epithelial chemokine (C-C motif) ligand 7 (CCL7) up-regulation. Intestinal epithelial cell (IEC)-specific CCL7 transgenic mice (CCL7tgIEC mice) showed markedly increased myosin light chain kinase (MLCK) phosphorylation and elevated gut permeability and bacterial translocation into the liver compared to wild-type mice. Global transcriptome analysis revealed that the expression of hepatic pro-inflammatory genes was enhanced in CCL7tgIEC mice compared to wild-type animals. Moreover, CCL7 overexpression in intestinal epithelial cells significantly augmented APAP-induced acute liver injury. Our data provides new evidence that dysfunction of CCL7-mediated gut barrier integrity may be an important contributor to APAP-induced hepatotoxicity. PMID: 31610172 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research