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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
gga-miR-21 modulates Mycoplasma gallisepticum (HS strain)-Induced inflammation via targeting MAP3K1 and activating
Yabo Zhao1, Mengyun Zou1, Yingfei Sun1
1Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Abstract:
Mycoplasma gallisepticum (MG) can target host cells and cause chronic respiratory disease (CRD) in chickens that is characterized by pMGA and concomitant. Although microRNAs (miRNAs) have been manifested are crucial regulatory noncoding RNAs with important effects on microbial pathogenesis and inflammatory response, how miRNAs regulate MG-induced inflammation remains to be discovered. The results showed that gga-miR-21 was up-regulated in MG-infected chicken embryonic lungs and MG infection of chicken embryo fibroblast cells (DF-1) compared with the control group. Overexpression of gga-miR-21 increased the inflammatory cytokines production, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) after MG infection, knockdown of gga-miR-21 had thoroughly inverse effects. Gene expression data combined with bioinformatics analysis and luciferase reporter assays demonstrated that mitogen-activated protein kinase kinase kinase 1(MAP3K1) was a novel target of gga-miR-21. The inhibition of MAP3K1 by gga-miR-21 resulted in the accumulation of NF-κB in the nucleus, which in turn generate higher inflammatory cytokines. Furthermore, upregulation of gga-miR-21 significantly inhibited MG propagation and promoted MG-infected DF-1 cells proliferation by increasing the cell cycle progression and suppressing cell apoptosis. Our study provides evidence for proinflammatory effects of gga-miR-21 which is mediated at least in part by targeting MAP3K1 in the MG-infected DF-1 cells. gga-miR-21 activates MAPKs and NF-κB signaling pathways via targeting MAP3K1, and then promotes the production of inflammatory cytokines and cell proliferation by increasing the cell cycle progression and suppressing cell apoptosis to defend against MG infection.
Insights
This study reveals that gga-miR-21 promotes inflammation in chickens infected with Mycoplasma gallisepticum (MG) by targeting MAP3K1. Upregulation of gga-miR-21 also inhibits MG spread and aids cell survival.
Area of Science:
- * Avian immunology
- * Molecular biology
- * Microbial pathogenesis
Background:
- * Mycoplasma gallisepticum (MG) causes chronic respiratory disease (CRD) in chickens.
- * MicroRNAs (miRNAs) are key regulators of inflammatory responses during infection.
- * The specific role of miRNAs in MG-induced inflammation is not fully understood.
Purpose of the Study:
- * To investigate the role of gga-miR-21 in chickens infected with MG.
- * To identify the molecular targets and pathways regulated by gga-miR-21 during MG infection.
- * To explore the potential of gga-miR-21 in controlling MG infection and its pathological effects.
Main Methods:
- * Quantification of gga-miR-21 expression in MG-infected chicken lungs and cells (DF-1).
- * Functional analysis of gga-miR-21 using overexpression and knockdown techniques.
- * Bioinformatics analysis, luciferase reporter assays, and gene expression analysis to identify targets and pathways (MAP3K1, NF-κB, MAPKs).
Main Results:
- * gga-miR-21 expression was significantly upregulated in MG-infected chicken tissues and cells.
- * Overexpression of gga-miR-21 enhanced inflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-8) and promoted cell proliferation, while knockdown had inverse effects.
- * MAP3K1 was identified as a direct target of gga-miR-21, leading to NF-κB activation and subsequent cytokine release. Upregulated gga-miR-21 inhibited MG propagation and promoted DF-1 cell proliferation.
Conclusions:
- * gga-miR-21 plays a significant role in the inflammatory response to MG infection in chickens.
- * The pro-inflammatory effects of gga-miR-21 are mediated, at least partly, by targeting MAP3K1, activating MAPKs and NF-κB signaling pathways.
- * gga-miR-21 exhibits potential as a therapeutic target for controlling MG infection by inhibiting bacterial spread and promoting host cell survival.
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