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Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation

Oncogene volume 18, pages 5455–5463 (1999)Cite this article

Abstract

Interferon Regulatory Factor (IRF)-1 is a multifunctional transcription factor, involved in cell growth regulation, pathogen response and immune activation. To identify novel gene targets that may contribute to IRF-1 mediated activities, RNA fingerprinting was performed using NIH3T3 cells that inducibly express a hybrid form of IRF-1 under tetracycline regulated control. Secretory leukocyte protease inhibitor (SLPI) – a regulator of inflammation and an inhibitor of the LPS response – was identified as a gene repressed after doxycycline induced IRF-1 expression. Preliminary analysis of the human SLPI promoter identified an ISRE-like site located within the −221 to −200 region to which IRF-1 binds and a second, putative IRF-1 binding site upstream of the TATA box. Furthermore, co-transfection studies demonstrated that SLPI expression was inhibited by IRF-1 co-expression. The identification of SLPI as a target of IRF-1 regulation reveals a unique involvement of IRF-1 in repression of gene transcription and assigns a novel role for IRF-1 in inflammation.

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References

  • Cha Y and Deisseroth AB. . 1994 J. Biol. Chem. 269: 5279–5287.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 150–159.

  • Clemens MJ and Elia A. . 1997 J. Interferon Cytokine Res. 17: 503–524.

  • Cohen L, Lacoste J, Parniak M, Daigneault L, Skup D and Hiscott J. . 1991 Cell Growth Differ. 2: 323–333.

  • Croen KD. . 1993 J. Clin. Invest. 91: 2446–2452.

  • Duncan GS, Mittrucker HW, Kagi D, Matsuyama T and Mak TW. . 1996 J. Exp. Med. 184: 2043–2048.

  • Fujita T, Sakakibara J, Sudo Y, Miyamoto M, Kimura Y and Taniguchi T. . 1988 EMBO J. 7: 3397–3405.

  • Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T and Taniguchi T. . 1989 Cell 58: 729–739.

  • Harada H, Kitagawa M, Tanaka N, Yamamoto H, Harada K, Ishihara M and Taniguchi T. . 1993 Science 259: 971–974.

  • Harada H, Takahashi E-I, Itoh S, Harada K, Hori T-A and Taniguchi T. . 1994 Mol. Cell Biol. 14: 1500–1509.

  • Jin F-Y, Nathan C, Radzioch D and Ding A. . 1997 Cell 88: 417–426.

  • Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ, Mak TW, Taniguchi T and Vilcek J. . 1994 Science 263: 1612–1615.

  • Karupiah G, Xie QW, Buller RM, Nathan C, Duarte C and MacMicking JD. . 1993 Science 261: 445–448.

  • Kimura T, Nakayama K, Penninger J, Kitagawa M, Harada H, Matsuyama T, Tanaka N, Kamijo R, Vilcek J, Mak TW and Taniguchi T. . 1994 Science 264: 1921–1924.

  • Lee CH, Igarashi Y, Hohman RJ, Kaulbach H, White MV and Kaliner MA. . 1993 Am. Rev. Resp. Dis. 147: 710–716.

  • Lin R, Ernsting B, Hirshfield IN, Matthews RG, Neidhardt FC, Clark RL and Newman EB. . 1992 J. Bacteriol. 174: 2779–2784.

  • Lin R, Mustafa A, Nguyen H and Hiscott J. . 1994 J. Biol. Chem. 269: 17542–17549.

  • Martin E, Nathan C and Xie Q-W. . 1994 J. Exp. Med. 180: 977–984.

  • Maruyama M, Hay JG, Yoshimura K, Chu C-S and Crystal RG. . 1994 J. Clin. Invest. 94: 368–375.

  • Matsuyama T, Kimura T, Kitagawa M, Watanabe N, Kundig T, Amakawa R, Kishihara K, Wakeham A, Potter J, Furlonger C, Narendran A, Suzuki H, Ohashi P, Paige C, Taniguchi T and Mak T. . 1993 Cell 75: 83–97.

  • Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T and Taniguchi T. . 1988 Cell 54: 903–913.

  • Nathan CF and Hibbs Jr JB. . 1991 Curr. Opin. Immunol. 3: 65–70.

  • Nguyen H, Hiscott J and Pitha PM. . 1997a Cyt. Growth Fact. Rev. 8: 293–312.

  • Nguyen H, Lin R and Hiscott J. . 1997b Oncogene 15: 1425–1435.

  • Nonkwello C, Ruf IK and Sample J. . 1997 J. Virol. 71: 6887–6897.

  • Penninger JM and Mak TW. . 1994 Immunol. Rev. 142: 231–272.

  • Pepin N, Roulston A, Lacoste J, Lin R and Hiscott J. . 1994 Virol. 204: 706–716.

  • Reis LFL, Harada H, Wolchok JD, Taniguchi T and Vilcek J. . 1992 EMBO J. 11: 185–193.

  • Reis LFL, Ruffner H, Stark G, Aguet M and Weissmann C. . 1994 EMBO J. 13: 4798–4806.

  • Sallenave JM, Shulmann J, Crossley J, Jordana M and Gauldie J. . 1994 Am. J. Resp. Cell Mol. Biol. 11: 733–741.

  • Taki S, Sato T, Ogasawara K, Fukuda T, Sato M, Hida S, Suzuki G, Mitsuyama M, Furuta T, Kojima S, Taniguchi T and Asano Y. . 1997 Immunity 6: 1–20.

  • Tanaka N, Kawakami T and Taniguchi T. . 1993 Mol. Cell Biol. 13: 4531–4538.

  • Taniguchi T, Lamphier MS and Tanaka N. . 1997 Biochim. Biophys. Acta Rev. Cancer 1333: M9–M17.

  • Thompson RC and Ohlsson K. . 1986 Proc. Natl. Acad. Sci. USA 83: 6692–6696.

  • Vaughan PS, Aziz F, van Wijnen AJ, Wu S, Harada H, Taniguchi T, Soprano KJ, Stein JL and Stein GS. . 1995 Nature 377: 362–365.

  • Vogelmeier C, Gillisen A and Buhl R. . 1996 Chest 110: 261S–266S.

  • Wang I-M, Blanco JCG, Tsai SY, Tsai M-J and Ozato K. . 1996 Mol. Cell Biol. 16: 6313–6324.

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Acknowledgements

This work was supported by grants from the Medical Research Council of Canada and the Canadian Foundation for AIDS Research (CANFAR). H Nguyen is the recipient of an FCAR studentship, R Lin is the recipient of a Fraser, Monat, MacPherson Fellowship from McGill University and J Hiscott is the recipient of a Senior Scientist Award from the Medical Research Council of Canada.

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Authors and Affiliations

  1. Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada

    Hannah Nguyen, Lindsay Teskey, Rongtuan Lin & John Hiscott

  2. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, H3T 1E2, Canada

    Hannah Nguyen, Lindsay Teskey & John Hiscott

  3. Department of Medicine, McGill University, Montreal, Quebec, H3T 1E2, Canada

    Rongtuan Lin & John Hiscott

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Nguyen, H., Teskey, L., Lin, R. et al. Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation. Oncogene 18, 5455–5463 (1999). https://doi.org/10.1038/sj.onc.1202924

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