Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced migration of UMUC-3 cells

• Published in: International journal of molecular medicine Vol. 30; no. 4; pp. 945 - 952
• Main Authors: LEE, SE-JUNG, KIM, WUN-JAE, MOON, SUNG-KWON
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2012; Spandidos Publications UK Ltd
• Subjects: Binding sites; Bladder cancer; bladder cancer cells; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cytokines; Enzyme Inhibitors - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Imidazoles - pharmacology; interleukin-28A; Interleukins - genetics; Interleukins - metabolism; Janus Kinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; matrix metalloproteinases-9; Medical research; Metastasis; migration; Neoplasms - genetics; Neoplasms - metabolism; NF-kappa B - metabolism; p38 MAPK; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Polyclonal antibodies; Pyridines - pharmacology; Signal Transduction - drug effects; STAT2 Transcription Factor - metabolism; Studies; Transcription Factor AP-1 - metabolism; Transcription factors; Tumors; Urinary Bladder - cytology
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2012.1064

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.