IL-5-induced migration via ERK1/2-mediated MMP-9 expression by inducing             activation of NF-κB in HT1376 cells.
Interleukin-5 (IL-5) plays an important role in the growth and differentiation             of human B cells and eosinophils. However, little is known about the effect of             IL-5 on cancer cells. In this study, we investigated the molecular mechanisms             involved in the IL-5-induced migration of HT1376 bladder cancer cells. Our results             indicated that IL-5 significantly enhanced migration and MMP-9 expression in HT1376             cells. We also found that IL-5 induces transcriptional activation of the binding             of NF-κB and AP-1, which are two important nuclear transcription factors that             are linked to MMP-9 expression in HT1376 cells. In subsequent experiments, we             found activation of ERK1/2 in IL-5-treated HT1376 cells. To examine the involvement             of the ERK1/2 signaling pathway on IL-5-induced cell responses, we pretreated             HT1376 cells with the ERK1/2 inhibitor U0126 followed by IL-5 treatment. The results             showed that U0126 treatment inhibited migration of IL-5-treated HT1376 cells.             Moreover, IL-5-stimulated MMP-9 expression was suppressed by the addition of U0126.             Inhibition of ERK1/2 function consistently rescued transcriptional activity of             NF-κB, without altering AP-1 activation, in IL-5-treated cells. Finally, inhibition             of the IL-5-specific receptor IL-5Rα by small interfering RNA (siRNA) suppressed             migration, ERK1/2 activation, MMP-9 expression and binding activation of NF-κB             in IL-5-treated HT1376 cells. The results of the present study indicate that the             IL-28A/IL-28AR1 dyad induces cell migration through ERK1/2-mediated expression             of MMP-9 by binding activation of NF-κB in bladder cancer cells. In conclusion,             these novel findings indicate that binding of IL-5 to IL-5Rα plays a critical             role in MMP-9 expression, which may be involved in the migration of bladder cancer.
Department of Biotechnology, Chungju National University, Chungju,                     Chungbuk 380-702, Republic of Korea.
Eo-Jin
EJ
Lee
Sung-Soo
SS
Park
Wun-Jae
WJ
Kim
Sung-Kwon
SK
Moon
D024506:5' Flanking Region; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053666:Interleukin-5 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D018808:Transcription Factor AP-1 / Q000378:metabolism
D002070:Butadienes; C508599:IL5 protein, human; C485918:IL5RA protein, human; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D016328:NF-kappa B; D009570:Nitriles; D018808:Transcription Factor AP-1; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9