Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3K/Akt Signal Pathway

• Published in: BioMed research international 2018-01, Vol.2018 (2018), p.1-11
• Main Authors: Bai, Shi, Wang, Huan, Zhao, Yan, Yuan, Wufeng, Fei, Xianming, Huang, Qinghua
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation analysis; Acute coronary syndromes; Adult; AKT protein; Arteriosclerosis; Atherosclerosis; Blood platelets; Blood Platelets - cytology; Blood Platelets - drug effects; Cardiac arrhythmia; Cardiovascular disease; Cell activation; Coronary vessels; COX-2 inhibitors; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase-2; Cytokines; Electron Transport Complex IV - metabolism; Enzyme-linked immunosorbent assay; Extracellular matrix; Female; Flow cytometry; Gene expression; Glycoproteins; Humans; Inflammation; Inflammatory response; Male; Mitogen-Activated Protein Kinases - metabolism; Monocyte chemoattractant protein 1; Monocytes; Monocytes - cytology; Monocytes - drug effects; mRNA; NF-κB protein; Papain; Papain - pharmacology; Pathogenesis; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Thrombin; Thrombolysis; Thrombosis; Tumor necrosis factor-α; Western blotting; Young Adult
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2018/3632084

Monocytes activation and subsequent inflammatory response mediated by monocyte-platelet aggregates (MPAs) formation play the key roles in the early pathogenesis of atherosclerosis (AS). Exploration of novel drugs to ameliorate MPAs formation-mediated monocytes activation would be helpful for the treatment of AS patients. Papain has definite pharmacological effects including antiplatelet, thrombolysis, and anti-inflammation. However, its effect on MPAs formation and the following monocytes activation remains vague. This study aimed to illustrate the underlying mechanisms of papain on MPAs formation-initiated monocytes activation in vitro. In this study, Papain, Cox-2 inhibitor (NS-398), and NF-κB agonist (TNF-α) were used as the treating agents, respectively. MPAs formation and activated monocytes were measured by flow cytometry (FCM). Cox-2 mRNA, MCP-1, and proteins of Cox-2 and NF-κB signal pathway were detected by qRT-PCR, ELISA, and western blotting, respectively. As we observed, papain exhibited the powerful inhibitory effects on thrombin-mediated MPAs formation and monocytes activation in a concentration-dependent manner as what Cox-2 inhibitor demonstrated. However, the inhibitory tendency was significantly reversed by TNF-α. We also discovered that both Cox-2 mRNA and protein expression as well as the release of MCP-1 of monocyte was inhibited by either papain or NS-398, but TNF-α stimulated Cox-2 expression and release of MCP-1. The results of western blotting assay indicated that thrombin-mediated proteins expression of MAPKs and PI3K/Akt signal pathway was inhibited by papain and NS-398. However, TNF-α notably abated the inhibitory effects of papain on the process of MPAs-initiated monocytes activation. Our findings suggest that papain can inhibit the MPAs formation-mediated activation of monocytes by inhibiting the MAPKs and PI3K/Akt signal pathway.