Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis.
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 C(4) 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 C(4) synthesis. Moreover, these data suggest that LTC4S and cys-LTs may be involved in acute systemic inflammatory responses such as fever and tachycardia.
Schröder
O
O
Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, 17 177 Stockholm, Sweden.
Sjöström
M
M
Qiu
H
H
Jakobsson
P-J
PJ
Haeggström
J Z
JZ
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D003545:Cysteine / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D005982:Glutathione Transferase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008861:Microsomes / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015854:Up-Regulation
D015289:Leukotrienes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C112381:cysteinyl-leukotriene; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D003545:Cysteine