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- Title
Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells.
- Authors
Sakai, Nozomu; Van Sweringen, Heather L; Belizaire, Ritha M; Quillin, Ralph Cutler; Schuster, Rebecca; Blanchard, John; Burns, Justin M; Tevar, Amit D; Edwards, Michael J; Lentsch, Alex B
- Abstract
Background and Aim: The purpose of the present study was to determine the effects of interleukin-37 (IL-37) on liver cells and on liver inflammation induced by hepatic ischemia/reperfusion (I/R). Methods: Mice were subjected to I/R. Some mice received recombinant IL-37 (IL-37) at the time of reperfusion. Serum levels of alanine aminotransferase, and liver myeloperoxidase content were assessed. Serum and liver tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemokine (KC) were also assessed. Hepatic reactive oxygen species (ROS) levels were assessed. For in vitro experiments, isolated hepatocytes and Kupffer cells were treated with IL-37 and inflammatory stimulants. Cytokine and chemokine production by these cells were assessed. Primary hepatocytes underwent induced cell injury and were treated with IL-37 concurrently. Hepatocyte cytotoxicity and Bcl-2 expression were determined. Isolated neutrophils were treated with TNF-α and IL-37 and neutrophil activation and respiratory burst were assessed. Results: IL-37 reduced hepatocyte injury and neutrophil accumulation in the liver after I/R. These effects were accompanied by reduced serum levels of TNF-α and MIP-2 and hepatic ROS levels. IL-37 significantly reduced MIP-2 and KC productions from lipopolysaccharide-stimulated hepatocytes and Kupffer cells. IL-37 significantly reduced cell death and increased Bcl-2 expression in hepatocytes. IL-37 significantly suppressed TNF-α-induced neutrophil activation. Conclusions: IL-37 is protective against hepatic I/R injury. These effects are related to the ability of IL-37 to reduce proinflammatory cytokine and chemokine production by hepatocytes and Kupffer cells as well as having a direct protective effect on hepatocytes. In addition, IL-37 contributes to reduce liver injury through suppression of neutrophil activity.
- Subjects
INTERLEUKINS; HEPATITIS; INFLAMMATION; LIVER cells; CHEMOKINES; ISCHEMIA
- Publication
Journal of Gastroenterology & Hepatology, 2012, Vol 27, Issue 10, p1609
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2012.07187.x