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.