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Activation of Toll-like receptors signaling in non-small cell lung cancer cell line induced by tumorassociated macrophages

  
@article{CJCR6224,
	author = {Xing Ke and Meng Wu and Jianfang Lou and Shuping Zhang and Peijun Huang and Ruihong Sun and Lei Huang and Erfu Xie and Fang Wang and Bing Gu},
	title = {Activation of Toll-like receptors signaling in non-small cell lung cancer cell line induced by tumorassociated macrophages},
	journal = {Chinese Journal of Cancer Research},
	volume = {27},
	number = {2},
	year = {2015},
	keywords = {},
	abstract = {Background: Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages (TAMs) and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors (TLRs) are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology.Methods: To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytokines in lung cancer cells, we established an in vitro coculture system using TAMs and human non-small cell lung cancer (NSCLC) cell line SPC-A1. Levels of interleukin (IL)-1β, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-A1 were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-A1 were also detected after the stimulation of TLRs agonists.Results: We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-13-acetate (PMA). Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being cocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8.Conclusions: These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.},
	issn = {1993-0631},	url = {http://cjcr.amegroups.com/article/view/6224}
}