Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis (original) (raw)

Abstract.

Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents, which play key roles in inflammatory and allergic diseases. The committed step in cys-LT biosynthesis is catalyzed by leukotriene C4 synthase (LTC4S) as well as microsomal glutathione S-transferase type 2 (MGST2) and type 3 (MGST3). Here we report that intraperitoneal injections of lipopolysaccharide in rats lead to a strong increase of LTC4S messenger RNA (mRNA) levels after approximately 1 h, particularly in the heart, brain, adrenal glands and liver, without any significant effect on MGST2 and MGST3 mRNA levels. After 6 h, LTC4S mRNA returns to basal levels, concomitant with a 4.9-, 4.0-, 2.9- and 2.3-fold induction of LTC4S protein in brain, heart, liver and adrenal gland, respectively. Hence, challenge with lipopolysaccharide in vivo causes an organ-selective, local priming for leukotriene C4 synthesis. Moreover, these data suggest that LTC4S and cys-LTs may be involved in acute systemic inflammatory responses such as fever and tachycardia.

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Author notes

  1. O. Schröder
    Present address: Division of Gastroenterology, 1st Department of Internal Medicine, ZAFES, Johann Wolfgang Goethe-University, 60590, Frankfurt, Germany

Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, 17 177, Stockholm, Sweden
    O. Schröder, M. Sjöström, H. Qiu, P. -J. Jakobsson & J. Z. Haeggström

Authors

  1. O. Schröder
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  2. M. Sjöström
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  3. H. Qiu
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  4. P. -J. Jakobsson
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  5. J. Z. Haeggström
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Corresponding author

Correspondence toJ. Z. Haeggström.

Additional information

Received 12 August 2004; received after revision 27 October 2004; accepted 1 November 2004

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Schröder, O., Sjöström, M., Qiu, H. et al. Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis.CMLS, Cell. Mol. Life Sci. 62, 87–94 (2005). https://doi.org/10.1007/s00018-004-4366-7

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