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Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages
Balázs Koscsó1, Balázs Csóka, Endre Kókai
11.Rutgers New Jersey Medical School, 185 South Orange Ave., University Heights, Newark, NJ 07103, USA. haskoge@njms.rutgers.edu.
Abstract:
The alternatively activated macrophage phenotype induced by IL-10 is called M2c. Adenosine is an endogenous purine nucleoside that accumulates in the extracellular space in response to metabolic disturbances, hypoxia, inflammation, physical damage, or apoptosis. As adenosine is known to regulate classically activated M1 and IL4- and IL-13-activated M2a macrophages, the goal of the present study was to explore its effects on M2c macrophages. We found that adenosine augmented the IL-10-induced expression of TIMP-1 and arginase-1 by the mouse macrophage cell line RAW 264.7 and by mouse BMDMs. The effects of AR stimulation on IL-10-induced TIMP-1 or arginase-1 expression were lacking in A2BAR KO macrophages. The role of A2BAR on TIMP-1 production of RAW 264.7 cells was confirmed with specific agonist BAY606583 and antagonist PSB0788. AR stimulation augmented IL-10-induced STAT3 phosphorylation in macrophages, and pharmacological inhibition or silencing of STAT3 using siRNA reduced the stimulatory effect of AR stimulation on TIMP-1 production. In contrast to its stimulatory effect on IL-10-induced STAT3 activation, adenosine inhibited IL-6-induced STAT3 phosphorylation and SAA3 expression. In conclusion, adenosine enhances IL-10-induced STAT3 signaling and M2c macrophage activation.
Insights
Adenosine enhances the M2c macrophage response, a key immune cell type. This purine nucleoside boosts interleukin-10 (IL-10)-induced signaling via the A2BAR receptor and STAT3, promoting M2c activation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Alternatively activated macrophages (M2c) are induced by IL-10.
- Adenosine, an endogenous nucleoside, regulates M1 and M2a macrophage phenotypes.
- The impact of adenosine on M2c macrophages remains largely unexplored.
Purpose of the Study:
- To investigate the effects of adenosine on M2c macrophages.
- To elucidate the signaling pathways involved in adenosine-mediated M2c regulation.
Main Methods:
- Utilized mouse macrophage cell lines (RAW 264.7) and primary bone marrow-derived macrophages (BMDMs).
- Employed knockout (KO) macrophages lacking the A2BAR.
- Administered specific agonists (BAY606583) and antagonists (PSB0788) for A2BAR.
- Investigated STAT3 phosphorylation and gene expression (TIMP-1, arginase-1, SAA3).
- Utilized siRNA for STAT3 silencing.
Main Results:
- Adenosine augmented IL-10-induced expression of TIMP-1 and arginase-1 in M2c macrophages.
- These effects were dependent on the A2BAR receptor.
- Adenosine enhanced IL-10-induced STAT3 phosphorylation.
- Adenosine inhibited IL-6-induced STAT3 phosphorylation and SAA3 expression.
Conclusions:
- Adenosine enhances IL-10-induced STAT3 signaling.
- Adenosine promotes the M2c macrophage activation phenotype.
- The A2BAR receptor and STAT3 pathway are critical for adenosine's effects on M2c macrophages.
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