title: PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice.
abstract: Macrophages play an important role in the pathogenesis of COPD. Macrophage polarization towards the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study, we combined cigarette smoke (CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice. We also demonstrated that decreased protein level for phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased total protein levels for phosphorylation -protein kinase B (p-AKT) in the lung tissue of emphysematous mice and in CSE-treated RAW264.7 cells. In both bone marrow-derived macrophages (BMDMs) from emphysematous mice and CSE-treated RAW264.7 cells, we observed by RT-PCR that the mRNA levels of M2 macrophage-related markers and cytokines were increased. Furthermore, M1 macrophage-related markers and cytokines were decreased. Meanwhile we treated BMDMs from emphysematous mice and CSE-treated RAW264.7 cells with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002), we observed a reduction in RNA levels of M2 macrophage-related markers and cytokines. In conclusion, we confirmed that macrophage M2 polarization was induced in emphysematous mice generated by CS exposure combined with intraperitoneal injection of CSE. We also showed that M2 polarization was mediated through PTEN/PI3k/AKT pathway activation.
authors.affiliation: Department of Respiratory Medicine, the Third XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Respiratory Medicine, the Third XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, the Third XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, the Third XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, the Third XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-9705-4632
authors.initials: S
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D037181:Lectins, C-Type / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012906:Smoke; D062789:Tobacco Products / Q000633:toxicity
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface; D012906:Smoke