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Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

Oncogene volume 23, pages 6603–6611 (2004)Cite this article

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-1β on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1β induced the IL-8 expression in a time- and concentration-dependent manner. IL-1β 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-1β also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1β-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)-κB sites were required for the IL-1β-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1β increased the DNA-binding activity of AP-1 and NF-κB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-κB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1β 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-κB signaling pathways are involved in the IL-1β-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation.

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Abbreviations

IL-8:

Interleukin-8

AP-1:

activator protein-1

C/EBP:

CCAAT/enhancer binding protein

NF-κB:

nuclear factor-κB

MAPK:

mitogen-activated protein kinase

ROS:

reactive oxygen species

Erk:

extracellular signal-related kinases

JNK:

c-Jun NH2-terminal kinases

NAC:

N-acetylcysteine

DCFDA:

5-(and 6)-carboxyl-2′,7′-dichlorodihydrofluorescein diacetate

CM:

conditioned media

References

  • Anthonsen MW, Andersen S, Solhaug A and Johansen B . (2001). J. Biol. Chem., 276, 35344–35351.

  • Baggiolini M, Moser B and Clark-Lewis I . (1994). Adv. Immunol., 55, 97–179.

  • Chen CY and Shyu AB . (1995). Trends Biochem. Sci., 20, 465–470.

  • Duval C, Cantero AV, Auge N, Mabile L, Thiers JC, Negre-Salvayre A and Salvayre R . (2003). Free Radic. Biol. Med., 35, 1589–1598.

  • Emrick MA, Hoofnagle AN, Miller AS, TenEyck LF and Ahn NG . (2001). J. Biol. Chem., 276, 46469–46479.

  • Folkman J . (1995). Nat. Med., 1, 27–31.

  • Ganesh S, Sier CF, Heerding MM, Van Krieken JH, Griffioen G, Welvaart K, Van de Velde CJ, Verheijen JH, Lamers CB and Verspaget HW . (1996). Cancer, 77, 1035–1043.

  • Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y and Han J . (2002). Science, 295, 1291–1294.

  • Goede V, Schmidt T, Kimmina S, Kozian D and Augustin HG . (1998). Lab. Invest., 78, 1385–1394.

  • Guan Z, Baier LD and Morrison AR . (1997). J. Biol. Chem., 272, 8083–8089.

  • Guiraldes E, Duarte I, Pena A, Godoy A, Espinosa MN, Bravo R, Larrain F, Schultz M and Harris P . (2001). J. Pediatr. Gastroenterol. Nutr., 33, 127–132.

  • Harris GK and Shi X . (2003). Mutat. Res., 533, 183–200.

  • Heidemann J, Ogawa H, Dwinell MB, Rafiee P, Maaser C, Gockel HR, Otterson MF, Ota DM, Lugering N, Domschke W and Binion DG . (2003). J. Biol. Chem., 278, 8508–8515.

  • Hirschi KK and D'Amore PA . (1997). EXS, 79, 419–428.

  • Hofmeister R, Wiegmann K, Korherr C, Bernardo K, Kronke M and Falk W . (1997). J. Biol. Chem., 272, 27730–27736.

  • Jung YD, Fan F, McConkey DJ, Jean ME, Liu W, Reinmuth N, Stoeltzing O, Ahmad SA, Parikh AA, Mukaida N and Ellis LM . (2002). Cytokine, 18, 206–213.

  • Kasahara T, Mukaida N, Yamashita K, Yagisawa H, Akahoshi T and Matsushima K . (1991). Immunology, 74, 60–67.

  • Katsuyama K and Hirata Y . (2001). J. Biochem., 129, 585–591.

  • Kitadai Y, Haruma K, Sumii K, Yamamoto S, Ue T, Yokozaki H, Yasui W, Ohmoto Y, Kajiyama G, Fidler IJ and Tahara E . (1998). Am. J. Pathol., 152, 93–100.

  • Kitadai Y, Takahashi Y, Haruma K, Naka K, Sumii K, Yokozaki H, Yasui W, Mukaida N, Ohmoto Y, Kajiyama G, Fidler IJ and Tahara E . (1999). Br. J. Cancer, 81, 647–653.

  • Klezovitch O, Edelstein C and Scanu AM . (2001). J. Biol. Chem., 276, 46864–46869.

  • Kunsch C, Lang RK, Rosen CA and Shannon MF . (1994). J. Immunol., 153, 153–164.

  • Lo YY, Conquer JA, Grinstein S and Cruz TF . (1998). J. Cell. Biochem., 69, 19–29.

  • Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y and Omata M . (2001). J. Biol. Chem., 276, 44856–44864.

  • Mastronarde JG, Monick MM, Mukaida N, Matsushima K and Hunninghake GW . (1998). J. Infect. Dis., 177, 1275–1281.

  • Mukaida N, Morita M, Ishikawa Y, Rice N, Okamoto S, Kasahara T and Matsushima K . (1994). J. Biol. Chem., 269, 13289–13295.

  • Ochiai A, Yasui W and Tahara E . (1985). Jpn. J.Cancer Res., 76, 1064–1071.

  • Ohba M, Shibanuma M, Kuroki T and Nose K . (1994). J. Cell Biol., 126, 1079–1088.

  • Rennekampff HO, Hansbrough JF, Kiessig V, Dore C, Sticherling M and Schroder JM . (2000). J. Surg. Res., 93, 41–54.

  • Schwarz M, Radeke HH, Resch K and Uciechowski P . (1997). Kidney Int., 52, 1521–1531.

  • Shin EY, Kim SY and Kim EG . (2001). Exp. Mol. Med., 33, 276–283.

  • Singh RK and Varney ML . (2000). Histol. Histopatho., 15, 843–849.

  • Sizemore N, Leung S and Stark GR . (1999). Mol. Cell. Biol., 19, 4798–4805.

  • Straubinger RK, Greiter A, McDonough SP, Gerold A, Scanziani E, Soldati S, Dailidiene D, Dailide G, Berg DE and Simpson KW . (2003). Infect. Immun., 71, 2693–2703.

  • Thannickal VJ and Fanburg BL . (1995). J. Biol. Chem., 270, 30334–30338.

  • Wang M, Furuta T, Takashima M, Futami H, Shirai N, Hanai H and Kaneko E . (1999). J. Gastroenterol., 34, 10–17.

  • Welsh N . (1996). J. Biol. Chem., 271, 8307–8312.

  • Wolf JS, Chen Z, Dong G, Sunwoo JB, Bancroft CC, Capo DE, Yeh NT, Mukaida N and Van Waes C . (2001). Clin. Cancer Res., 7, 1812–1820.

  • Wu LL, Chiou CC, Chang PY and Wu JT . (2004). Clin. Chim. Acta., 339, 1–9.

  • Yasumoto K, Okamoto S, Mukaida N, Murakami S, Mai M and Matsushima K . (1992). J. Biol. Chem., 267, 22506–22511.

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Acknowledgements

We are very grateful to Dr Eiichi Tahara (Hiroshima University, Japan) for TMK-1 cells, to Dr Natalie Ahn (University of Colorado, USA) for the MEK-1 construct and to Dr Jiahuai Han (Scripps Research Institute, USA) for the P38 MAPK construct. This work was supported by a grant (PF0320504-00) from the Plant Diversity Research Center of the 21st Century Frontier Program Funded by the Ministry of Science and Technology of Korean government.

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Authors and Affiliations

  1. Department of Biochemistry, Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, 5 Hakdong, Kwangju, 501-190, Korea

    Young S Hwang, Min Jeong, Jung S Park, Mi H Kim, Dae B Lee, Boo A Shin, Hyeong R Kim, Bong W Ahn & Young D Jung

  2. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan

    Naofumi Mukaida

  3. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 444, Houston, 77030-4009, TX, USA

    Lee M Ellis

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  1. Young S Hwang
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Hwang, Y., Jeong, M., Park, J. et al. Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells. Oncogene 23, 6603–6611 (2004). https://doi.org/10.1038/sj.onc.1207867

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