title: Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced             migration of UMUC-3 cells.
abstract: Although interleukin-28A (IL-28A) is believed to have an antiviral effect, its role in tumor migration requires further examination. The present study was intended to verify the effect of IL-28A on the migration of UMUC-3 bladder cancer cells. IL-28A and its receptor IL-28AR1 mRNA were detected in UMUC-3 cells. Although exogenous IL-28A showed no effect on cell proliferation, a wound-healing migration assay showed that the migration of UMUC-3 cells was induced by IL-28A. Furthermore, treatment of the cells with IL-28A significantly promoted MMP-9 expression via binding activities of NF-κB and AP-1. IL-28A also induced the activation of p38 MAPK and Jak2-Stat2 signaling. Using the p38 MAPK inhibitor SB203580 and the dominant-negative plasmid DN-p38, we found evidence that the inhibition of p38 MAPK signaling suppressed the effects of IL-28A including wound-healing migration and MMP-9 expression by activation of NF-κB and AP-1 binding in UMUC-3 cells. However, Jak-2 inhibition by AG490 did not affect IL-28A-induced migration of UMUC-3 cells. Collectively, we suggest for the first time that the p38 MAPK pathway mediates IL-28A-induced cell migration through MMP-9 expression by activating NF-κB and AP-1 binding motifs.
authors: Department of Biotechnology, Chungju National University, Chungju,                     Chungbuk 380-702, Republic of Korea.
authors: Se-Jung
authors: SJ
authors: Lee
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000095022:Interferon Lambda
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D007378:Interleukins; D053614:Janus Kinase 2; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D011725:Pyridines; D050795:STAT2 Transcription Factor; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494084:STAT2 protein, human; C507924:JAK2 protein, human; C093642:SB 203580