Adenosine receptor activation promotes macrophage class switching from LPS-induced acute inflammatory M1 to

Velayudhan Jayasree Devi1, Achuthan Radhika2, Prabath Gopalakrishnan Biju1

  • 1Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram, Kerala 695581, India.

Immunobiology
|March 2, 2023
PubMed

Insights

Activation of adenosine receptors shifts macrophages from a pro-inflammatory M1 state to an anti-inflammatory M2 state. This suggests adenosine receptor targeting may be a therapeutic strategy for acute inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Lipopolysaccharide (LPS) induces a pro-inflammatory M1 macrophage phenotype.
  • Adenosine, a purine nucleoside, plays a key role in this inflammatory response.
  • Macrophage phenotype plasticity is crucial in regulating inflammation.

Purpose of the Study:

  • To investigate the role of adenosine receptor modulation in macrophage phenotype switching.
  • To determine if adenosine receptor activation can shift macrophages from M1 to M2 phenotype.
  • To explore adenosine receptor targeting as a potential therapeutic strategy for inflammation.

Main Methods:

  • Used the mouse macrophage cell line RAW 264.7.
  • Stimulated cells with Lipopolysaccharide (LPS) (1 μg/ml).
  • Activated adenosine receptors using the agonist NECA (1 μM).

Main Results:

  • Adenosine receptor stimulation suppressed LPS-induced pro-inflammatory mediators (cytokines, ROS, nitrite).
  • M1 markers (CD38, CD83) significantly decreased, while M2 markers (Th2 cytokines, Arginase, TIMP, CD206) increased.
  • Demonstrated a time-course profile of adenosine receptor-mediated phenotype switching.

Conclusions:

  • Adenosine receptor activation programs macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype.
  • Adenosine receptor modulation is a significant factor in macrophage phenotype plasticity.
  • Targeting adenosine receptors presents a promising therapeutic avenue for managing acute inflammation.

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