In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 11 ( 2022-11-21), p. e0278059-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0278059
DOI:
10.1371/journal.pone.0278059.g001
DOI:
10.1371/journal.pone.0278059.g002
DOI:
10.1371/journal.pone.0278059.g003
DOI:
10.1371/journal.pone.0278059.g004
DOI:
10.1371/journal.pone.0278059.g005
DOI:
10.1371/journal.pone.0278059.g006
DOI:
10.1371/journal.pone.0278059.t001
DOI:
10.1371/journal.pone.0278059.t002
DOI:
10.1371/journal.pone.0278059.s001
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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