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The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to Pseudomonas aeruginosa

Chithra K Muraleedharan1, Sharon A McClellan1, Sandamali A Ekanayaka1

  • 1Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, USA.

Journal of Innate Immunity
|January 10, 2019
PubMed

Insights

The miR-183/96/182 cluster regulates macrophage immune responses. This microRNA cluster impacts the production of inflammatory molecules and reactive species, crucial for innate immunity against pathogens like Pseudomonas aeruginosa.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Macrophages are key innate immune cells involved in pathogen defense and adaptive immunity modulation.
  • MicroRNAs (miRNAs) are critical gene regulators, but their specific roles in macrophage function remain incompletely understood.
  • The miR-183/96/182 cluster is conserved and its function in macrophages requires further investigation.

Purpose of the Study:

  • To investigate the role of the conserved miR-183/96/182 cluster in regulating macrophage (Mϕ) function.
  • To determine the impact of miR-183/96/182 on Mϕ production of reactive nitrogen (RNS) and oxygen species (ROS).
  • To elucidate the effect of miR-183/96/182 on inflammatory responses to Pseudomonas aeruginosa (PA) and lipopolysaccharide (LPS).

Main Methods:

  • Utilized Mϕ-like Raw264.7 cells and primary peritoneal macrophages from wild-type and miR-183/96/182-knockout mice.
  • Assessed cytokine production following PA or LPS stimulation.
  • Measured nitrite and ROS production.
  • Identified downstream target genes, including DAP12 and Nox2.

Main Results:

  • Knockdown of miR-183/96/182 decreased proinflammatory cytokine production in response to PA/LPS.
  • Peritoneal macrophages from knockout mice showed reduced responsiveness to PA/LPS but increased basal cytokine levels.
  • Overexpression of miR-183/96/182 led to reduced nitrite and ROS production.
  • DAP12 and Nox2 were identified as downstream targets of miR-183/96/182.

Conclusions:

  • The miR-183/96/182 cluster plays a significant role in modulating macrophage function.
  • This miRNA cluster regulates inflammatory responses and the production of reactive species.
  • miR-183/96/182 exerts global control over macrophage functions via diverse downstream targets.
Keywords:
DAP12DNAX-activating protein 12 kDaInflammationLipopolysaccharidesMacrophagesMicroRNANADPH oxidase 2Nox2Pseudomonas aeruginosaReactive nitrogen speciesReactive oxygen speciesmiR-183/96/182 cluster

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