Eicosapentaenoic acid (EPA) reduced lipopolysaccharide-stimulated inflammatory response of RAW264.7 cells via the miR-125b-5p/CREB axis

Inflammation represents an adaptive physiological response of body immune system to infection or tissue damage, which may be regulated by food supplementation. Eicosapentaenoic acid (EPA) has multi-functions and its anti-inflammatory effect has gained great attention. This study aimed to address the exact molecular mechanism underlying its inflammatory control. The results showed that EPA decreased lipopolysaccharide-induced inflammatory response in RAW264.7 cells by modulating the production of cellular cytokines. In addition, EPA downregulated miR-125b-5p, which showed pro-inflammatory effect and its forced expression attenuated EPA's anti-inflammatory activity. Moreover, the cAMP-responsive element-binding protein (CREB) is targeted by miR-125b-5p. CREB overexpression reduced inflammation probably via modulating the PGC-1α/NF-κB pathway, which resembled the effect of EPA pre-treatment. Therefore, EPA exhibited anti-inflammatory activity by targeting the miR-125b-5p/CREB axis, which modulated the production of inflammatory mediators probably via transcription control. This study provides insights into microRNA-mediated action mechanism and facilitates the relief of inflammation-associated diseases by food ingredients.