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Published on: May 31, 2018
Papain ameliorates monocyte-platelet aggregate formation-mediated inflammatory responses in monocytes by upregulating
Lei Jiang1, Chan Xu2, Yan Zhao3
1Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Background:
MicroRNA-146a (miRNA-146a) is a nuclear factor κB (NF-κB)-inducible and inflammation-sensitive miRNA, while papain elicits anti-inflammatory effects by inhibiting monocyte-platelet aggregate (MPA)-mediated NF-κB pathway activation in monocytes. This study aimed to demonstrate the underlying effects of papain on MPA formation-initiated miRNA-146a expression and subsequent action in monocytes.
Methods:
THP-1 cells were exposed to papain, miRNA-146a mimic and inhibitor, NF-κB inhibitor (BAY11-7082), and platelets. Flow cytometry was used to measure the MPA formation-initiated monocyte activation. Levels of miRNA-146a, cyclooxygenase 2 (COX-2) mRNA and protein, and monocyte chemoattractant protein 1 (MCP-1) were analyzed in monocytes by RT-PCR, western blot, and ELISA.
Results:
The NF-κB inhibitor and miRNA-146a mimics upregulated miRNA-146a expression but suppressed subsequent monocyte activation and expression of COX-2 and MCP-1. Following exposure to papain, the enhanced miRNA-146a transcription induced by MPA-formation was found along with significant inhibition of monocyte activation in a dose-dependent manner. However, the inhibitory tendency was significantly reversed by miRNA-146a inhibitors. Expression of COX-2 mRNA and protein, as well as MCP-1, was inhibited in monocytes by papain, whereas miRNA-146a inhibitors promoted COX-2 and MCP-1 expression.
Conclusion:
Our findings suggest that papain can inhibit MPA formation-mediated expression of inflammatory mediators in activated monocytes by upregulating miRNA-146a transcription.
Insights
Papain reduces inflammation by increasing microRNA-146a (miRNA-146a) levels, which suppresses inflammatory responses in monocytes activated by monocyte-platelet aggregates (MPAs). This highlights miRNA-146a's role in papain's anti-inflammatory action.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-146a (miRNA-146a) is induced by inflammation and nuclear factor κB (NF-κB).
- Papain exhibits anti-inflammatory properties by inhibiting NF-κB pathway activation in monocyte-platelet aggregates (MPAs).
Purpose of the Study:
- To investigate papain's effect on miRNA-146a expression initiated by MPA formation.
- To elucidate the role of miRNA-146a in papain's anti-inflammatory mechanism in monocytes.
Main Methods:
- THP-1 cells were treated with papain, miRNA-146a mimics/inhibitors, NF-κB inhibitor, and platelets.
- Monocyte activation and MPA formation were assessed using flow cytometry.
- Levels of miRNA-146a, cyclooxygenase 2 (COX-2), and monocyte chemoattractant protein 1 (MCP-1) were quantified via RT-PCR, western blot, and ELISA.
Main Results:
- NF-κB inhibition and miRNA-146a mimics increased miRNA-146a and decreased monocyte activation, COX-2, and MCP-1.
- Papain dose-dependently inhibited MPA-induced monocyte activation and inflammatory mediator expression.
- miRNA-146a inhibitors reversed papain's inhibitory effects and increased COX-2 and MCP-1 expression.
Conclusions:
- Papain enhances miRNA-146a transcription, thereby suppressing inflammatory mediators.
- Papain's anti-inflammatory effects in monocytes are mediated through the upregulation of miRNA-146a.

