M2 polarized macrophages induced by CSE promote proliferation, migration, and invasion of alveolar basal epithelial cells.

Cigarette smoking plays an important role in the genesis of lung cancer, and tumor-associated macrophages (TAMs) are believed to accelerate the process. We therefore sought to clarify the relationship between cigarette smoking, TAMs and tumorigenesis. We treated macrophages (THP-1) with cigarette smoke extract (CSE) and found that the mRNA levels of IL-6, IL-10, IL-12 and TNF-α decreased, while TGF-β mRNA levels increased. CSE significantly inhibited the phagocytic ability of macrophages, as assessed by flow cytometric analysis of FITC-dextran internalization. JAK2/STAT3 was significantly activated by CSE, as determined by Western blot analysis. When the scavenger receptor CD163, a specific marker of M2 macrophages, was analyzed by flow cytometry, its expression was significantly increased. After inducing M2 polarization of THP-1 cells, we co-cultured macrophages and alveolar basal epithelial cells (A549). The proliferation of A549 cells was detected by the MTT assay and cell cycle analysis, while their migration and invasion were detected by scratch wound assay and transwell assay. The results showed that the proliferation, migration and invasion of A549 cells were significantly promoted by M2 macrophages but were slightly inhibited by CSE. In conclusion, we demonstrated that macrophage M2 polarization induced by CSE promotes proliferation, migration, and invasion of alveolar basal epithelial cells.