MicroRNA-155 enhances ocular inflammation after Pseudomonas aeruginosa infection (158.11)

Abstract

Abstract Abstract: As a gene regulator, microRNA (miR)-155 plays an important role in both autoimmune inflammation as well as antiviral innate immunity. However, the role of miR-155 in Pseudomonas aeruginosa (PA) keratitis remains unknown. Our study demonstrated that miR-155 expression levels were significantly up-regulated in PA-infected vs normal human corneas as well as Macrophages derived from PBMC. Furthermore, in vivo studies showed that miR-155 expression was significantly increased in PA-infected corneas of C57BL/6 (B6) mice. Inhibition of miR-155 led to reduced ocular disease after PA infection, by down-regulating pro-inflammatory cytokine (e.g., IL-1β, IFN-γ, IL-6, IL-12) production. In vitro studies also demonstrated that PA challenge induced miR-155 expression in a time- and dose-dependent manner in peritoneal Macrophages and RAW264.7 cells. The induction of miR-155 was dependent on TLR2, TLR4, TLR9, through NF-κB, IKK, JNK and PI3K, but not P38 or ERK pathways. Moreover, overexpression of miR-155 significantly decreased Macrophage-mediated phagocytosis and intracellular bacterial killing of PA, by down-regulating expression of mannose receptor (MR) and complement receptor 3 (CR3). miR-155 overexpression also enhanced the production of pro-inflammatory cytokines including IFN-γ, IL-1β, IL-6, IL-12, IL-17A, but reduced anti-inflammatory cytokine IL-10 expression. Collectively, these data indicated that miR-155 functions as an inflammatory amplifier in PA keratitis.