Heparin inhibits lipopolysaccharide-induced inflammation via inducing caveolin-1 and activating the p38/mitogen-activated protein kinase pathway in murine peritoneal macrophages

Abstract

Heparin is a soluble glycosaminoglycan largely used as an anti-coagulant drug and with well known anti-inflammatory effects. However, heparin is currently not used as an anti-inflammatory agent in the clinic due to a risk of bleeding as well as its complex mechanism of action. The underlying mechanism of the anti-inflammatory action of heparin and its effector targets have remained to be fully elucidated. The present study confirmed the anti-inflammatory effects of heparin in lipopolysaccharide (LPS)-induced murine peritoneal macrophages through decreasing the levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-8 and IL-1β. Caveolin-1 participated in the anti-inflammatory process and it was able to be induced by heparin. Transfection of small interfering RNA of caveolin-1 into murine peritoneal macrophages attenuated the anti-inflammatory effects of heparin. Furthermore, following caveolin-1 silencing, the p38/mitogen-activated protein kinase (MAPK) pathway was still able to be activated by heparin, while the extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways were inhibited. In conclusion, these results suggested that heparin inhibits LPS-induced inflammation via inducing caveolin-1 and activating the p38/MAPK pathway in murine peritoneal macrophages. Revealing the anti-inflammatory mechanisms of heparin will aid in its development for clinical treatment in the future.