title: Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2/STAT3 pathway.
abstract: Cigarette smoking is a major pathogenic factor in lung cancer. Macrophages play an important role in host defense and adaptive immunity. These cells display diverse phenotypes for performing different functions. M2 type macrophages usually exhibit immunosuppressive and tumor-promoting characteristics. Although macrophage polarization toward the M2 phenotype has been observed in the lungs of cigarette smokers, the molecular basis of the process remains unclear. In this study, we evaluated the possible mechanisms for the polarization of mouse macrophages that are induced by cigarette smoking (CS) or cigarette smoke extract (CSE). The results showed that exposure to CSE suppressed the production of reactive oxygen species (ROS) and nitric oxide (NO) and down-regulated the phagocytic ability of Ana-1 cells. The CD163 expressions on the surface of macrophages from different sources were significantly increased in in vivo and in vitro studies. The M1 macrophage cytokines TNF-α, IL-12p40 and enzyme iNOS decreased in the culture supernatant, and their mRNA levels decreased depending on the time and concentration of CSE. In contrast, the M2 phenotype macrophage cytokines IL-10, IL-6, TGF-β1 and TGF-β2 were up-regulated. Moreover, phosphorylation of JAK2 and STAT3 was observed after the Ana-1 cells were treated with CSE. In addition, pretreating the Ana-1 cells with the STAT3 phosphorylation inhibitor WP1066 inhibited the CSE-induced CD163 expression, increased the mRNA level of IL-10 and significantly decreased the mRNA level of IL-12. In conclusion, we demonstrated that the M2 polarization of macrophages induced by CS could be mediated through JAK2/STAT3 pathway activation.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China; The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: Hengfei
authors.initials: H
authors.lastname: Shi
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: Guopu
authors.initials: G
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2