IL-23 and IL-17A are not involved in hepatic/ischemia reperfusion injury in mouse and man
Journal Title: Journal of Clinical and Translational Research - Year 2015, Vol 1, Issue 3
Abstract
Background: Hepatic ischemia and reperfusion (I/R) is common in liver surgery and transplantation and compromises postoperative liver function. Hepatic I/R injury is characterized by sterile inflammation that contributes to hepatocellular necrosis. Many immune cells and cytokines have been implicated in hepatic I/R injury. However, the role and relevance of IL-23 and IL-17A remains controversial in literature. Aim: To determine whether the IL-23/IL-17A signaling axis is activated in hepatic I/R using a triple-level experimental approach (in vitro, in vivo, and clinical). Methods: IL-23 and IL-17A were assayed by ELISA in the supernatant fractions of cultured murine (RAW 264.7) macrophages that were activated by supernatant fractions of necrotic cultured mouse (AML12) hepatocytes. Similarly, levels of these cytokines were determined in plasma samples and liver tissue of mice (N = 85) subjected to partial (70%) liver I/R. Finally, IL-23 and IL-17A were assayed in plasma samples obtained from a controlled cohort of liver resection patients who were either subjected to I/R (N = 27) or not (N = 13). Results: Activated macrophages did not produce IL-23 in response to supernatant of necrotic AML12 hepatocytes. IL-23 and IL-17A were not elevated in mice subjected hepatic I/R and were not elevated in serum from patients subjected to I/R during liver resection. Conclusion: IL-23 and IL-17A are not involved in hepatic I/R injury in mouse and man. Relevance for patients: If IL-23 and IL-17A were to mediate hepatocellular injury following I/R, these cytokines would constitute potential therapeutic targets. Since this study has revealed that IL-23 and IL-17A do not play a role in hepatic I/R, other pathways and therapeutic targets should be considered when developing modalities aimed at reducing hepatic I/R injury.
Authors and Affiliations
Pim B. Olthof, Rowan F. van Golen, Megan J. Reiniers, Milan Kos, Lindy K. Alles, Martinus A. Maas, Joanne Verheij, Thomas M. van Gulik, Michal Heger
Keywords
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