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Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models.

Li E, Xu Z, Zhao H, Sun Z, Wang L, Guo Z, Zhao Y, Gao Z, Wang Q - Oncotarget (2015)

Bottom Line: Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture.Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats.We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.

ABSTRACT
We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

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Related in: MedlinePlus

Cell proliferation and colony formation data on human bronchial epithelial cells after BaP treatmentA, Cell proliferation assay. 16HBE cells at passage 30 were subjected to the cell proliferation assay after exposure to BaP. B, Colony formation assay. 16HBE cells at passages 30 and 40 were subjected to the colony formation assay after exposure to BaP. *p < 0.05 compared to the DMSO group, #p < 0.05 compared to the BaP group, ▲p < 0.05 compared to the BaP + coculture with macrophages group.
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Figure 4: Cell proliferation and colony formation data on human bronchial epithelial cells after BaP treatmentA, Cell proliferation assay. 16HBE cells at passage 30 were subjected to the cell proliferation assay after exposure to BaP. B, Colony formation assay. 16HBE cells at passages 30 and 40 were subjected to the colony formation assay after exposure to BaP. *p < 0.05 compared to the DMSO group, #p < 0.05 compared to the BaP group, ▲p < 0.05 compared to the BaP + coculture with macrophages group.

Mentions: Tumorigenicity is characterized by growth promotion. As shown in Fig. 4A, BaP treatment could stimulate bronchial epithelial cell proliferation, while macrophages also enhanced this effect. As expected, blockage of cytokine IL-6 or TNF-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression inhibited cell proliferation.


Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models.

Li E, Xu Z, Zhao H, Sun Z, Wang L, Guo Z, Zhao Y, Gao Z, Wang Q - Oncotarget (2015)

Cell proliferation and colony formation data on human bronchial epithelial cells after BaP treatmentA, Cell proliferation assay. 16HBE cells at passage 30 were subjected to the cell proliferation assay after exposure to BaP. B, Colony formation assay. 16HBE cells at passages 30 and 40 were subjected to the colony formation assay after exposure to BaP. *p < 0.05 compared to the DMSO group, #p < 0.05 compared to the BaP group, ▲p < 0.05 compared to the BaP + coculture with macrophages group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496191&req=5

Figure 4: Cell proliferation and colony formation data on human bronchial epithelial cells after BaP treatmentA, Cell proliferation assay. 16HBE cells at passage 30 were subjected to the cell proliferation assay after exposure to BaP. B, Colony formation assay. 16HBE cells at passages 30 and 40 were subjected to the colony formation assay after exposure to BaP. *p < 0.05 compared to the DMSO group, #p < 0.05 compared to the BaP group, ▲p < 0.05 compared to the BaP + coculture with macrophages group.
Mentions: Tumorigenicity is characterized by growth promotion. As shown in Fig. 4A, BaP treatment could stimulate bronchial epithelial cell proliferation, while macrophages also enhanced this effect. As expected, blockage of cytokine IL-6 or TNF-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression inhibited cell proliferation.

Bottom Line: Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture.Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats.We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.

ABSTRACT
We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

No MeSH data available.


Related in: MedlinePlus