| First Author | Kong D | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 10 | Pages | 2209-26 |
| PubMed ID | 27621415 | Mgi Jnum | J:237274 |
| Mgi Id | MGI:5811932 | Doi | 10.1084/jem.20160459 |
| Citation | Kong D, et al. (2016) PKA regulatory IIalpha subunit is essential for PGD2-mediated resolution of inflammation. J Exp Med 213(10):2209-26 |
| abstractText | The kinetic participation of macrophages is critical for inflammatory resolution and recovery from myocardial infarction (MI), particularly with respect to the transition from the M1 to the M2 phenotype; however, the underlying mechanisms are poorly understood. In this study, we found that the deletion of prostaglandin (PG) D2 receptor subtype 1 (DP1) in macrophages retarded M2 polarization, antiinflammatory cytokine production, and resolution in different inflammatory models, including the MI model. DP1 deletion up-regulated proinflammatory genes expression via JAK2/STAT1 signaling in macrophages, whereas its activation facilitated binding of the separated PKA regulatory IIalpha subunit (PRKAR2A) to the transmembrane domain of IFN-gamma receptor, suppressed JAK2-STAT1 axis-mediated M1 polarization, and promoted resolution. PRKAR2A deficiency attenuated DP1 activation-mediated M2 polarization and resolution of inflammation. Collectively, PGD2-DP1 axis-induced M2 polarization facilitates resolution of inflammation through the PRKAR2A-mediated suppression of JAK2/STAT1 signaling. These observations indicate that macrophage DP1 activation represents a promising strategy in the management of inflammation-associated diseases, including post-MI healing. |
