miR-185-5p Regulates Inflammation and Phagocytosis through CDC42/JNK Pathway in Macrophages

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Macrophage activation is central to chronic inflammation and inflammatory diseases.
• MicroRNA-185-5p (miR-185-5p) is implicated in inflammatory conditions, but its role in macrophage activation is unknown.

Purpose of the Study:

• To investigate the regulatory role of miR-185-5p in macrophage pro-inflammatory activation.
• To elucidate the molecular mechanisms underlying miR-185-5p's function in inflammation.

Main Methods:

• Analysis of macrophage miRNA expression datasets (GEO).
• Overexpression and inhibition of miR-185-5p in LPS-stimulated RAW264.7 macrophages.
• Assessment of pro-inflammatory cytokine expression and phagocytosis.
• Investigation of CDC42 protein levels and its regulation by miR-185-5p.
• Utilizing CDC42 inhibitor (CASIN) and assessing MAPK/JNK pathway activity.

Main Results:

• miR-185-5p was downregulated in macrophage miRNA datasets.
• miR-185-5p overexpression reduced pro-inflammatory cytokines and suppressed phagocytosis.
• miR-185-5p inhibitors enhanced LPS-induced pro-inflammatory responses.
• miR-185-5p negatively regulated CDC42 protein expression.
• CDC42 inhibition reversed the pro-inflammatory effects of miR-185-5p inhibitors via the MAPK/JNK pathway.

Conclusions:

• miR-185-5p exhibits anti-inflammatory functions in LPS-induced macrophages.
• The anti-inflammatory effect is mediated, at least partially, through the CDC42/JNK pathway.
• Findings provide insights into the miR-185-5p regulatory network in macrophage inflammation and its relevance to atherosclerotic inflammation.