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.

Unfractionated Heparin Alleviates Human Lung Endothelial Barrier Dysfunction Induced by High Mobility Group Box 1 Through Regulation of P38–GSK3β–Snail Signaling Pathway

“…We also found that UFH could downregulate the p38 phosphorylation induced by HMGB1. Inhibition of lipopolysaccharide-induced p38 activation by heparin has also been reported in endothelial cells [32]. Moreover, we observed there is a synergistic effect of UFH and p38 inhibitor in stabilizing barrier function of HPMECs.…”

Low‐intensity pulsed ultrasound attenuates cardiac inflammation of CVB3‐induced viral myocarditis via regulation of caveolin‐1 and MAPK pathways

“…Whether there was a relationship between caveolin‐1 and MAPK signallings under LIPUS treatment was investigated by transfecting RAW264.7 with caveolin‐1siRNA. It has been reported that Caveolin‐1 regulated inflammatory response through MAPK signallings . Elena Tourkina et al.…”

“…Caveolin‐1, a major component of the plasma membrane microdomains, has been identified in cellular mechanotransduction system sensing the stimulation of LIPUS treatment. It was well known that caveolin‐1 was expressed in various immune cells, including macrophages, dendritic cells and lymphocytes and acted as a potent immunomodulatory molecule via regulating the mitogen‐activated protein kinases (MAPK) family members …”

“…It was well known that caveolin-1 was expressed in various immune cells, including macrophages, dendritic cells and lymphocytes and acted as a potent immunomodulatory molecule via regulating the mitogen-activated protein kinases (MAPK) family members. [15][16][17][18] In this study, we aimed to investigate two unknown entities, whether the LIPUS treatment could regulate the aggressive immunological response of CVB3-induced myocarditis, and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effect.…”

Unfractionated heparin ameliorates pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization in acute lung injury

“…The p38 MAPK pathway is involved in various biological functions, including endothelial barrier function in response to exogenous and endogenous stimuli [ 15 , 16 ]. We observed that UFH regulated anti-inflammatory activity by inhibiting p38 MAPK activation [ 17 , 18 ]. Hence, we investigated whether the p38 MAPK pathway was involved in UFH-mediated attenuation of LPS-induced MT disassembly and endothelial barrier dysfunction.…”