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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-\u03b3\/LPS-induced macrophage polarization to M1-like as shown by increased Arg-1 associated to lower levels of M1 cytokines (TNF-\u03b1\/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.<\/jats:p>","DOI":"10.3390\/cells9010128","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T10:34:46Z","timestamp":1578306886000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-6006","authenticated-orcid":false,"given":"Graziele L.","family":"Negreiros-Lima","sequence":"first","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1813-0212","authenticated-orcid":false,"given":"K\u00e1tia M.","family":"Lima","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-8814","authenticated-orcid":false,"given":"Isabella Z.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Lorrayne O.","family":"Jardim","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8188-3738","authenticated-orcid":false,"given":"Juliana P.","family":"Vago","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5817-7808","authenticated-orcid":false,"given":"L\u00edvia Cristina R.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-2324","authenticated-orcid":false,"given":"Vanessa","family":"Pinho","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, 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