Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2/STAT3 pathway

• Published in: PloS one Vol. 9; no. 9; p. e107063
• Main Authors: Yuan, Fengjiao, Fu, Xiao, Shi, Hengfei, Chen, Guopu, Dong, Ping, Zhang, Weiyun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.09.2014; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Animals; Biology and Life Sciences; Blotting, Western; CD163 antigen; Cell culture; Cells, Cultured; Cigarette smoke; Cigarette smoking; Cigarettes; Cytokines; Cytokines - genetics; Cytokines - metabolism; Drug dosages; Epigenetics; Flow Cytometry; Gene expression; Genotype & phenotype; Immunity; Immunosuppression; In vivo methods and tests; Interleukin 10; Interleukin 12; Interleukin 6; Janus kinase 2; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Laboratories; Lung cancer; Lung diseases; Lungs; Macrophages; Macrophages, Alveolar - cytology; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Male; Medical prognosis; Medical schools; Medicine; Mice; Mice, Inbred BALB C; mRNA; Neutrophils; Nicotiana - chemistry; Nitric oxide; Nitric-oxide synthase; Oxygen; Phagocytes; Phenotypes; Phosphorylation; Phosphorylation - drug effects; Plant Extracts - pharmacology; Polarization; Reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Rodents; Signal Transduction - drug effects; Smoke; Smoking; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transforming growth factor-b1; Tumor necrosis factor-α; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107063

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.