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Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis.
- Source :
-
Cells [Cells] 2020 Jan 06; Vol. 9 (1). Date of Electronic Publication: 2020 Jan 06. - Publication Year :
- 2020
-
Abstract
- Macrophages are central to inflammation resolution, an active process aimed at restoring tissue homeostasis following an inflammatory response. Here, the effects of db-cAMP on macrophage phenotype and function were investigated. Injection of db-cAMP into the pleural cavity of mice induced monocytes recruitment in a manner dependent on PKA and CCR2/CCL2 pathways. Furthermore, db-cAMP promoted reprogramming of bone-marrow-derived macrophages to a M2 phenotype as seen by increased Arg-1/CD206/Ym-1 expression and IL-10 levels (M2 markers). Db-cAMP also showed a synergistic effect with IL-4 in inducing STAT-3 phosphorylation and Arg-1 expression. Importantly, db-cAMP prevented IFN-γ/LPS-induced macrophage polarization to M1-like as shown by increased Arg-1 associated to lower levels of M1 cytokines (TNF-α/IL-6) and p-STAT1. In vivo, db-cAMP reduced the number of M1 macrophages induced by LPS injection without changes in M2 and Mres numbers. Moreover, db-cAMP enhanced efferocytosis of apoptotic neutrophils in a PKA-dependent manner and increased the expression of Annexin A1 and CD36, two molecules associated with efferocytosis. Finally, inhibition of endogenous PKA during LPS-induced pleurisy impaired the physiological resolution of inflammation. Taken together, the results suggest that cAMP is involved in the major functions of macrophages, such as nonphlogistic recruitment, reprogramming and efferocytosis, all key processes for inflammation resolution.
- Subjects :
- Animals
Annexin A1 metabolism
Apoptosis drug effects
Arginase metabolism
Bucladesine pharmacology
CD36 Antigens metabolism
Cell Polarity drug effects
Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors
Inflammation pathology
Interleukin-4 metabolism
Isoquinolines pharmacology
Lipopolysaccharides
Macrophages drug effects
Male
Mice, Inbred BALB C
Models, Biological
Monocytes drug effects
Monocytes metabolism
Neutrophils drug effects
Neutrophils metabolism
Neutrophils pathology
Phenotype
Phosphorylation drug effects
Pleural Cavity metabolism
Receptors, CCR2 metabolism
STAT3 Transcription Factor metabolism
Sulfonamides pharmacology
Time Factors
Cellular Reprogramming drug effects
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Macrophages metabolism
Phagocytosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 31935860
- Full Text :
- https://doi.org/10.3390/cells9010128