MiR-184 Inhibits Inflammation Through Targeting Toll-Like Receptor 4 (TLR4)/NLR Family Pyrin Domain Containing 3 (NLRP3) Signaling Pathway in Neonatal Purulent Meningitis

Abstract

Neonatal purulent meningitis (NPM) leads to higher mortality and neurological sequelae rates. miR184 involves in inflammation and tumor, but the role of miR-184 in NPM remains unclear. NPM patients and non-intracranial infected neonates were collected and miR-184 expression in cerebrospinal fluid was assessed by real-time PCR. The Neuro-2a cell line was cultured and divided into control group, inflammation group (treated with LPS), and miR-184 inhibitor group, which was transfected with miR-184 inhibitor on the basis of inflammation followed by analysis of miR-184 and TLR4 expression by Real time PCR, Caspase 3 activity, cell proliferation by MTT assay, secretion of IL-1β and IL-6 by ELISA, NLRP3 expression by real time PCR and western blot, and Caspase-1 p20 and NF- B level by western blot. miR-184 expression level was significantly increased in cerebrospinal fluid of NPM group (P < 0 05) and also elevated in inflammation group along with significantly inhibited cell proliferation was inhibited, increased Caspase 3 activity, IL-1β and IL-6 secretion, and decreased TLR4, NLRP3, Caspase-1 p20 and NFκ- B expression (P < 0 05). miR-184 inhibitor significantly down-regulated miR-184 expression in the inflammation group, promoted cell proliferation, decreased Caspase 3 activity, IL-1β and IL-6 secretion, and increased TLR4, NLRP3, Caspase1 p20 and NF- κB expression (P < 0 05). miR-184 expression is increased in neonatal purulent meningitis and it can inhibit inflammation by targeting TLR4/NLRP3 signaling pathway, leading to amelioration of the progression of neonatal purulent meningitis.