April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
MicroRNA-155 Enhances Ocular Inflammation after Pseudomonas aeruginosa Infection
Author Affiliations & Notes
  • Xi Huang
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan
    Microbiology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China
  • Anping Peng
    Microbiology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China
  • Xinxin Nie
    Microbiology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China
  • Mingxia Sun
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan
  • Minhao Wu
    Microbiology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China
  • Ping Zhang
    Microbiology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China
  • Footnotes
    Commercial Relationships  Xi Huang, None; Anping Peng, None; Xinxin Nie, None; Mingxia Sun, None; Minhao Wu, None; Ping Zhang, None
  • Footnotes
    Support  NIH grants R01 EY019021 and P30 EY04068; NSFC (National Natural Science Foundation of China) grants U0832006 and 30972763.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5814. doi:
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    • Get Citation

      Xi Huang, Anping Peng, Xinxin Nie, Mingxia Sun, Minhao Wu, Ping Zhang; MicroRNA-155 Enhances Ocular Inflammation after Pseudomonas aeruginosa Infection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5814.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To explore the role of microRNA (miR)-155 in Pseudomonas aeruginosa (PA) keratitis.

Methods: : Ocular infection, isolation of human peripheral blood mononuclear cell (PBMC), isolation of murine peritoneal macrophage (Mϕ), in vivo miR-155 inhibition, cell culture assays, phagocytosis assay, and real time RT-PCR.

Results: : miR-155 expression levels were significantly up-regulated in PA-infected vs normal human corneas as well as Mϕ 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 Mϕ 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 Mϕ-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.

Conclusions: : Induction of miR-155 is dependent on TLR2, TLR4, TLR9, through NF-ΚB, IKK, JNK and PI3K signal pathway after PA infection. miR-155 amplifies ocular inflammation after PA infection by reducing bacterial phagocytosis and enhancing production of pro-inflammatory cytokines.

Keywords: inflammation • immunomodulation/immunoregulation • cornea: basic science 
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