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Interleukin-1beta stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells.
Oncogene. 2004 Aug 26; 23(39):6603-11.O

Abstract

Recent studies have suggested that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. In this study, the effect of IL-1beta on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1beta induced the IL-8 expression in a time- and concentration-dependent manner. IL-1beta induced the activation of extracellular signal-regulated kinases-1/2 and P38 mitogen-activated protein kinase (MAPK), but not the activation of c-jun amino-terminal kinse and Akt. Specific inhibitors of MEK-1 (PD980590) and P38 MAPK (SB203580) were found to suppress the IL-8 expression and the IL-8 promoter activity. Expression of vectors encoding a mutated-type MEK-1 and P38 MAPK resulted in decrease in the IL-8 promoter activity. IL-1beta also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1beta-induced ROS production and IL-8 expression. In addition, exogenous H2O2 could induce the IL-8 expression. Deletional and site-directed mutagenesis studies on the IL-8 promoter revealed that activator protein-1 (AP-1) and nuclear factor (NF)-kappaB sites were required for the IL-1beta-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1beta increased the DNA-binding activity of AP-1 and NF-kappaB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1beta could remarkably stimulate the in vitro growth of HUVEC and this effect was partially abrogated by IL-8-neutralizing antibodies. The above results suggest that MAPK-AP-1 and ROS-NF-kappaB signaling pathways are involved in the IL-1beta-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation.

Authors+Show Affiliations

Department of Biochemistry, Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, 5 Hakdong, Kwangju, 501-190, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15208668

Citation

Hwang, Young S., et al. "Interleukin-1beta Stimulates IL-8 Expression Through MAP Kinase and ROS Signaling in Human Gastric Carcinoma Cells." Oncogene, vol. 23, no. 39, 2004, pp. 6603-11.
Hwang YS, Jeong M, Park JS, et al. Interleukin-1beta stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells. Oncogene. 2004;23(39):6603-11.
Hwang, Y. S., Jeong, M., Park, J. S., Kim, M. H., Lee, D. B., Shin, B. A., Mukaida, N., Ellis, L. M., Kim, H. R., Ahn, B. W., & Jung, Y. D. (2004). Interleukin-1beta stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells. Oncogene, 23(39), 6603-11.
Hwang YS, et al. Interleukin-1beta Stimulates IL-8 Expression Through MAP Kinase and ROS Signaling in Human Gastric Carcinoma Cells. Oncogene. 2004 Aug 26;23(39):6603-11. PubMed PMID: 15208668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1beta stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells. AU - Hwang,Young S, AU - Jeong,Min, AU - Park,Jung S, AU - Kim,Mi H, AU - Lee,Dae B, AU - Shin,Boo A, AU - Mukaida,Naofumi, AU - Ellis,Lee M, AU - Kim,Hyeong R, AU - Ahn,Bong W, AU - Jung,Young D, PY - 2004/6/23/pubmed PY - 2004/9/17/medline PY - 2004/6/23/entrez SP - 6603 EP - 11 JF - Oncogene JO - Oncogene VL - 23 IS - 39 N2 - Recent studies have suggested that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. In this study, the effect of IL-1beta on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1beta induced the IL-8 expression in a time- and concentration-dependent manner. IL-1beta induced the activation of extracellular signal-regulated kinases-1/2 and P38 mitogen-activated protein kinase (MAPK), but not the activation of c-jun amino-terminal kinse and Akt. Specific inhibitors of MEK-1 (PD980590) and P38 MAPK (SB203580) were found to suppress the IL-8 expression and the IL-8 promoter activity. Expression of vectors encoding a mutated-type MEK-1 and P38 MAPK resulted in decrease in the IL-8 promoter activity. IL-1beta also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1beta-induced ROS production and IL-8 expression. In addition, exogenous H2O2 could induce the IL-8 expression. Deletional and site-directed mutagenesis studies on the IL-8 promoter revealed that activator protein-1 (AP-1) and nuclear factor (NF)-kappaB sites were required for the IL-1beta-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1beta increased the DNA-binding activity of AP-1 and NF-kappaB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1beta could remarkably stimulate the in vitro growth of HUVEC and this effect was partially abrogated by IL-8-neutralizing antibodies. The above results suggest that MAPK-AP-1 and ROS-NF-kappaB signaling pathways are involved in the IL-1beta-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/15208668/Interleukin_1beta_stimulates_IL_8_expression_through_MAP_kinase_and_ROS_signaling_in_human_gastric_carcinoma_cells_ L2 - https://doi.org/10.1038/sj.onc.1207867 DB - PRIME DP - Unbound Medicine ER -