Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3KAkt Signal Pathway

Abstract EN

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.