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However, mechanisms driving COX-2 overexpression remained elusive. Previously, transforming growth factor-\u03b2 (TGF-\u03b2) signaling after BMT was shown to promote hypomethylation of the COX-2 gene. Here, we provide mechanistic insight into how this occurs and show that TGF-\u03b2 induces microRNA (miR)-29b while decreasing DNA methyltransferases (DNMT)1, DNMT3a, and DNMT3b in AMs after BMT. De novo DNMT3a and DNMT3b were decreased upon transient transfection of miR-29b, resulting in decreased methylation of the COX-2 promoter and induction of COX-2. As a consequence, miR-29b-driven upregulation of COX-2 promoted AM dysfunction, and transfection of BMT AMs with a miR-29b inhibitor rescued the bacterial-killing defect. MiR-29b-mediated defects in BMT AMs were dependent on increased levels of PGE<jats:sub>2<\/jats:sub>, as miR-29b-transfected AMs treated with a novel E prostanoid receptor 2 antagonist abrogated the impaired bacterial killing. We also demonstrate that patients that have undergone HSCT exhibit increased miR-29b; thus these studies highlight miR-29b in driving defective AM responses and identify this miRNA as a potential therapeutic target.<\/jats:p>","DOI":"10.1152\/ajplung.00283.2014","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T09:10:30Z","timestamp":1414833030000},"page":"L86-L95","source":"Crossref","is-referenced-by-count":19,"title":["Transforming growth factor-\u03b2 induces microRNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation"],"prefix":"10.1152","volume":"308","author":[{"given":"Racquel","family":"Domingo-Gonzalez","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, Michigan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Wilke","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care 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