|Title:||Autocrine and paracrine regulation of interleukin-8 expression in lung cancer cells||Authors:||Yao P.-L.
|Issue Date:||2005||Journal Volume:||32||Journal Issue:||6||Start page/Pages:||540-547||Source:||American Journal of Respiratory Cell and Molecular Biology||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)-α and IL-1α could induce IL-8 expression in lung cancer cells in a dose-dependent manner. Neutralization with TNF-α and IL-1α antibodies in cocultures decreased the levels of IL-8 expression in sensitized lung cancer cells. Nuclear factor-κB 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-κB pathway and modulated by TNF-α and IL-1α.
|ISSN:||1044-1549||DOI:||10.1165/rcmb.2004-0223OC||SDG/Keyword:||acetylsalicylic acid; dexamethasone; immunoglobulin enhancer binding protein; interleukin 1 antibody; interleukin 1alpha; interleukin 1alpha antibody; interleukin 8; messenger RNA; pentoxifylline; phorbol 13 acetate 12 myristate; pyrrolidine dithiocarbamate; recombinant tumor necrosis factor alpha; tumor necrosis factor alpha antibody; unclassified drug; angiogenesis; article; autocrine effect; cancer cell culture; cell interaction; coculture; cytokine production; dose response; gel mobility shift assay; human; human cell; lung alveolus macrophage; lung cancer; macrophage; paracrine signaling; sensitization; Antibodies; Autocrine Communication; Carcinogens; Coculture Techniques; Dose-Response Relationship, Drug; Fibroblasts; Gene Expression; Humans; Interleukin-1; Interleukin-8; Lung Neoplasms; Macrophages, Alveolar; Monocytes; NF-kappa B; Paracrine Communication; Pneumonia; Respiratory Mucosa; RNA, Messenger; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha
|Appears in Collections:||醫學系|
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