دورية أكاديمية
A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury.
| العنوان: | A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury. |
|---|---|
| المؤلفون: | Kleinschmidt, Dörte1, Giannou, Anastasios D.1, McGee, Heather M.2, Kempski, Jan1, Steglich, Babett1,3, Huber, Francis Jessica1, Ernst, Thomas Michael4, Shiri, Ahmad Mustafa1, Wegscheid, Claudia5, Tasika, Elena5, Hübener, Peter1, Huber, Philipp1, Bedke, Tanja1, Steffens, Niklas1, Agalioti, Theodora3, Fuchs, Tobias6, Noll, Jill7, Lotter, Hannelore7, Tiegs, Gisa5, Lohse, Ansgar W.1 |
| المصدر: | Journal of Immunology. 12/15/2017, Vol. 199 Issue 12, p4078-4090. 13p. |
| مصطلحات موضوعية: | *GROWTH factors, *LIVER diseases, *ISCHEMIA, *LYMPHOCYTES, *INTERLEUKIN-22, *ACETAMINOPHEN |
| مستخلص: | Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury. IL-22 binding protein (IL-22BP, IL-22Ra2) is a soluble inhibitor of IL-22 that regulates IL-22 activity. However, the significance of endogenous IL-22BP in acute liver injury is unknown. We hypothesized that IL-22BP may play a role in acute liver injury. To test this hypothesis, we used Il22bp-deficient mice and murine models of acute liver damage induced by ischemia reperfusion and N-acetyl-p-aminophenol (acetaminophen) administration. We found that Il22bp-deficient mice were more susceptible to acute liver damage in both models. We used Il22 3 Il22bp double-deficient mice to show that this effect is indeed due to uncontrolled IL-22 activity. We could demonstrate mechanistically increased expression of Cxcl10 by hepatocytes, and consequently increased infiltration of inflammatory CD11b+Ly6C+ monocytes into the liver in Il22bp-deficient mice upon liver damage. Accordingly, neutralization of CXCL10 reversed the increased disease susceptibility of Il22bp-deficient mice. In conclusion, our data indicate that IL-22BP plays a protective role in acute liver damage, via controlling IL-22-induced Cxcl10 expression. [ABSTRACT FROM AUTHOR] |
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All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury. IL-22 binding protein (IL-22BP, IL-22Ra2) is a soluble inhibitor of IL-22 that regulates IL-22 activity. However, the significance of endogenous IL-22BP in acute liver injury is unknown. We hypothesized that IL-22BP may play a role in acute liver injury. To test this hypothesis, we used Il22bp-deficient mice and murine models of acute liver damage induced by ischemia reperfusion and N-acetyl-p-aminophenol (acetaminophen) administration. We found that Il22bp-deficient mice were more susceptible to acute liver damage in both models. We used Il22 3 Il22bp double-deficient mice to show that this effect is indeed due to uncontrolled IL-22 activity. We could demonstrate mechanistically increased expression of Cxcl10 by hepatocytes, and consequently increased infiltration of inflammatory CD11b+Ly6C+ monocytes into the liver in Il22bp-deficient mice upon liver damage. Accordingly, neutralization of CXCL10 reversed the increased disease susceptibility of Il22bp-deficient mice. In conclusion, our data indicate that IL-22BP plays a protective role in acute liver damage, via controlling IL-22-induced Cxcl10 expression. [ABSTRACT FROM AUTHOR] ) |
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