Abstract
Inflammation is a local immune response to 'foreign' molecules, infection and injury. Leukotriene B4, a potent chemotactic agent that initiates, coordinates, sustains and amplifies the inflammatory response, is shown to be an activating ligand for the transcription factor PPARα. Because PPARα regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B4 in the liver. Thus PPARα offers a new route to the development of anti- or pro-inflammatory reagents.
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References
Ford-Hutchinson, A. W. Crit. Rev. Immunol. 10, 1–11 (1990).
Samuelsson, B., Dahlén, S.-E., Lindgren, J. A., Rouzer, C. A. & Serhan, C. N. Science 237, 1171–1176 (1987).
Jedlitschky, G. et al. J. Biol. Chem. 266, 24763–24772 (1991).
Kikuta, Y. et al. J. Biol. Chem. 268, 9376–9380 (1993).
Harper, T. W., Garrity, M. J. & Murphy, R. C. J. Biol. Chem. 261, 5414–5418 (1986).
von Schacky, C., Kiefl, R., Marcus, A. J., Breokman, M. J. & Kaminski, W. E. Biochem. Biophys. Acta 1166, 20–24 (1993).
Couve, A. O., Koenig, C. & Santos, M. J. Exp. Cell. Res. 202, 541–544 (1992).
Jedlitschky, G., Mayatepek, E. & Keppler, D. Adv. Enzyme Reg. 33, 181–194 (1993).
Serhan, C. N., Fridovich, J., Geotzl, E. J., Dunham, P. B. & Weissmann, G. J. Biol. Chem. 257, 4746–4752 (1982).
Rola-Pleszcynynski, M. in Cell-cell Interactions in the Release of Inflammatory Mediators (eds Serhan, C. N. & Wong, P. Y.) 205–221 (Plenum, New York, 1991).
Lemberger, T., Desvergne, B. & Wahli, W. Annu. Rev. Cell Dev. Biol. 12, 335–363 (1996).
Desvergne, B. & Wahli, W. in Inducible Transcription Vol. 1 (ed. Bæuerle, P.) 142–176 (Birkhäuser, Boston, 1995).
Issemann, I. & Green, S. Nature 347, 645–650 (1990).
Kliewer, S. A. et al. Proc. Natl Acad. Sci. USA 91, 7355–7359 (1994).
Göttlicher, M. et al. Biochem. Pharmacol. 46, 2177–2184 (1993).
Keller, H. et al. Proc. Natl Acad. Sci. USA 90, 2160–2164 (1993).
Yu, K. et al. J. Biol. Chem. 270, 23975–23983 (1995).
Dreyer, C. et al. Cell 68, 879–887 (1992).
Amri, E. Z., Bonino, F., Ailhaud, G., Abumrad, N. A. & Grimaldi, P. A. J. Biol. Chem. 270, 2367–2371 (1995).
Chen, F., Law, S. W. & O'Malley, B. W. Biochem. Biophys. Res. Commun. 196, 671–677 (1993).
Zhu, Y., Alvares, K., Huang, Q., Rao, M. S. & Reddy, J. K. J. Biol. Chem. 268, 26817–26820 (1993).
Aperlo, C., Pognonec, P., Saladin, R., Auwerx, J. & Boulukos, K. E. Gene 162, 297–302 (1995).
Greene, M. E. et al. Gene Expr. 4, 281–299 (1995).
Schmidt, A. et al. Mol. Endocrinol. 6, 1634–1641 (1992).
Sher, Y., Yi, H. F., McBride, O. W. & Gonzalez, F. J. Biochemistry 32, 5598–5604 (1993).
Kliewer, S. A., Umesono, K., Noonon, D. J., Heyman, R. A. & Evans, R. M. Nature 358, 771–774 (1992).
Lee, S. S.-T. et al. Mol. Cell. Biol. 15, 3012–3022 (1995).
Braissant, O., Foufelle, F., Scotto, C., Dauça, M. & Wahli, W. Endocrinology 137, 354–366 (1996).
Kliewer, S. A. et al. Cell 83, 813–819 (1995).
Forman, B. M. et al. Cell 83, 803–812 (1995).
Lehmann, J. M. et al. J. Biol. Chem. 270, 12953–12956 (1995).
Taylor, B. M. & Sun, F. F. Biochem. Pharm. 34, 3495–3498 (1985).
Lemberger, T. et al. J. Biol. Chem. 271, 1764–1769 (1966).
Gad, S. C., Dunn, B. J., Dobbs, D. W., Reilly, C. & Walsh, R. D. Toxicol. Appl. Pharmacol. 84, 93–114 (1986).
Opas, E. E., Bonney, R. J., Humes, J. L. J. Invest. Dermatol. 84, 253–256 (1985).
Carlson, R. P., O'Neill-Davis, L., Cheng, J. & Lewis, A. J. Agents Act. 17, 197–204 (1985).
Smith, W. L. Biochem. J. 259, 315–324 (1989).
Chen, X.-Y., Sheller, J. R., Johnson, E. N. & Funk, C. D. Nature 372, 179–182 (1994).
Hertz, R., Berman, I., Keppler, D. & Bar-Tana, J. Eur. J. Biochem. 235, 242–247 (1996).
Yu, K. et al. J. Biol. Chem. 270, 23975–23983 (1995).
Peters, J. M. et al. Mol. Pharmacol. 50, 67–94 (1996).
Miller, A. M., van Bekkum, D. W., Kobb, S. M., McCrohan, M. B. & Knaan-Shanzer, S. Prost. Leuk. Fatty acids 49, 561–563 (1993).
Hussain, K. et al. Am. J. Physiol. 266 C243–253 (1994).
Krey, G. et al. J. Ster. Biochem. Mol. Biol. 47, 65–73 (1993).
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Devchand, P., Keller, H., Peters, J. et al. The PPARα–leukotriene B4 pathway to inflammation control. Nature 384, 39–43 (1996). https://doi.org/10.1038/384039a0
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DOI: https://doi.org/10.1038/384039a0
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