Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis.
We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.
Engblom
David
D
Division of Cell Biology, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden.
Saha
Sipra
S
Engström
Linda
L
Westman
Marie
M
Audoly
Laurent P
LP
Jakobsson
Per-Johan
PJ
Blomqvist
Anders
A
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000134:cerebrospinal fluid / Q000494:pharmacology; D004195:Disease Models, Animal; D005334:Fever / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008861:Microsomes / Q000201:enzymology*; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone