miR ‐19a‐3p and miR ‐19b‐3p Promote Microglia Activation Associated With Neuroinflammation

ABSTRACT

Neuroinflammation, driven by microglia activation and the production of pro‐inflammatory cytokines, has been implicated in several neurological diseases and neuropathic pain. MicroRNAs (miRNAs) have emerged as important regulators of neuroinflammatory processes. Prior studies identified elevated levels of circulating miR‐19a and miR‐19b in individuals living with chronic pain following spinal cord injury (SCI). In this study, we wanted to determine whether miR‐19a and miR‐19b have a direct effect on microglia activation, specifically pro‐inflammatory activation, associated with neuroinflammation. Microglia were activated by inflammatory stimuli in the presence of miR‐19a or miR‐19b mimics, and assessed for the expression of cytokines, chemokines, and effector molecules. The results show that miR‐19a or miR‐19b mimics increased the expression of pro‐inflammatory cytokines, chemokines, and effector molecules in microglia. The results also showed decreased expression of suppressor of cytokine signaling (SOCS) proteins, namely SOCS1 and SOCS3, in activated microglia with miR‐19a and miR‐19b mimics. Additionally, enhanced signaling through the NFκB and Jak pathways was observed with increased NFkB‐p65 and JAK1 phosphorylation in the presence of miR‐19a and miR‐19b mimics. Further results show that miR‐19a and miR‐19b inhibitors reversed these effects on activated microglia. Overall, our results demonstrate that miR‐19a or miR‐19b increased the expression of pro‐inflammatory cytokines, chemokines, and effector molecules in activated microglia. These results indicate that miR‐19a and miR‐19b can enhance microglia activation and associated inflammatory responses, which may have implications for conditions associated with neuroinflammation.