title: Autocrine and paracrine regulation of interleukin-8 expression in lung cancer cells.
abstract: We had previously demonstrated that lung cancer cells, upon contact with macrophages, could be induced to secrete angiogenic factors to promote tumor angiogenesis. In this study, we focused on the paracrine and autocrine regulation of interleukin (IL)-8 expression in sensitized lung cancer cells after interacting with macrophages. We found that the IL-8 mRNA expression in lung cancer cells significantly increased after coculture with phorbol myristate acetate-treated THP-1 cells and human primary lung macrophages. Fresh lung cancer CL1-5 cells cocultured with macrophage-sensitized lung cancer cells still had a 35% of increase in IL-8 mRNA expression. The addition of anti-inflammatory agents pyrrolidine dithiocarbamate, pentoxifylline, aspirin, and dexamethasone could completely suppress the expression of IL-8 mRNA in fresh/sensitized lung cancer cell cocultures. Human recombinant tumor necrosis factor (TNF)-alpha and IL-1alpha could induce IL-8 expression in lung cancer cells in a dose-dependent manner. Neutralization with TNF-alpha and IL-1alpha antibodies in cocultures decreased the levels of IL-8 expression in sensitized lung cancer cells. Nuclear factor-kappaB transcriptional activity was also suppressed by the same antibodies, as confirmed by a reporter gene assay and the electrophoretic mobility shift assay. Our results highly suggest that both autocrine and paracrine regulation are involved in IL-8 expression of lung cancer cells cocultured with macrophage. Also, the regulations of IL-8 expression in lung cancer cells were through the nuclear factor-kappaB pathway and modulated by TNF-alpha and IL-1alpha.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan 100, ROC.
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Yao
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lin
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Wang
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Huang
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Liao
authors.forename: Shan-Shue
authors.initials: SS
authors.lastname: Wang
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology; D002273:Carcinogens / Q000494:pharmacology; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics* / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000906:Antibodies; D002273:Carcinogens; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate