American Society for Investigative Pathology, June 2014, Vol 6, No. 2

Hot off the Press

 

Interleukin-17A Synergistically Enhances Bile Acid-induced Inflammation during Obstructive Cholestasis

 

O'Brien KM, Allen KM, Rockwell CE, Towery K, Luyendyk JP, Copple BL.

 

Am J Pathol 2013, 183(5):1498-507

 

“Interleukin-17A Synergistically Enhances Bile Acid-induced Inflammation during Obstructive Cholestasis,” submitted by O’Brien et al, reports that bile acids are novel activators of the Interleukin-23/Interleukin-17A (IL-23/IL-17A) axis in cholestatic liver disease. Utilizing the 0.3% cholic acid diet, we showed that bile acid induces hepatic IL-23 expression localized in hepatocytes. Confirming our in vivo data, primary murine hepatocytes treated with taurocholic acid also had an increase in IL-23 expression that was dependent on AKT and JNK. To further investigate the role of the IL-23/IL-17A axis during cholestasis, we treated mice with a neutralizing antibody against IL-17A and subjected them to bile duct ligation, a model of obstructive cholestasis. Our results demonstrated that IL-17A contributes to hepatocellular injury and inflammation during cholestasis. In addition, primary hepatocytes treated with recombinant IL-17A in combination with taurocholic acid had a synergistic enhancement of the pro-inflammatory cytokine, macrophage inflammatory protein-2 (MIP-2). Overall, we have shown that the IL-23/IL-17A axis is a key regulator of the neutrophilic inflammatory response in cholestatic liver disease.