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The novel activated microglia/macrophage WAP domain protein, AMWAP, acts as a counter-regulator of proinflammatory

Marcus Karlstetter1, Yana Walczak, Karin Weigelt

  • 1Institute of Human Genetics, University of Regensburg, Regensburg, The Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)
|August 17, 2010
PubMed

Insights

Researchers identified a new protein, activated microglia/macrophage WAP domain protein (AMWAP), that helps regulate immune responses in the brain and retina. AMWAP reduces inflammation and may play a role in neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Microgliosis, the activation of microglia, is prevalent in neurodegenerative diseases like inherited retinal dystrophies.
  • Identifying genes that regulate microglial activation is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To discover novel genes involved in microglial activation using a mouse model of inherited retinal degeneration.
  • To characterize the function and regulation of a newly identified microglia/macrophage-restricted protein.

Main Methods:

  • DNA-microarray analysis of retinal microglia from wild-type and retinoschisin-deficient mice.
  • Cloning and characterization of the novel gene AMWAP.
  • Investigated AMWAP expression and regulation via TLR ligands, IFN-gamma, NF-kappaB, and PU.1.
  • Assessed functional roles through overexpression and knockdown studies, including cytokine analysis, cell migration, adhesion, and antimicrobial activity.

Main Results:

  • A novel gene, AMWAP, was identified and found to be expressed in microglia and macrophages.
  • AMWAP transcription is induced by TLR ligands and IFN-gamma, regulated by NF-kappaB and PU.1.
  • AMWAP overexpression suppressed pro-inflammatory cytokines (IL-6, IL-1beta) and enhanced alternative activation markers (arginase 1, Cd206).
  • AMWAP knockdown increased pro-inflammatory markers and decreased alternative activation markers.
  • AMWAP exhibited anti-serine protease activity, reduced cell migration, increased adhesion, and possessed antimicrobial properties.

Conclusions:

  • AMWAP acts as a counter-regulator of pro-inflammatory microglia/macrophage activation.
  • AMWAP is a potential modulator of innate immunity, particularly relevant in the context of neurodegeneration.
  • The findings suggest AMWAP as a therapeutic target for neuroinflammatory conditions.

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