The PPARalpha-leukotriene B4 pathway to inflammation control.
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 PPARalpha. Because PPARalpha 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 PPARalpha offers a new route to the development of anti- or pro-inflammatory reagents.
Devchand
P R
PR
Institut de Biologie animale, Université de Lausanne, Switzerland.
Keller
H
H
Peters
J M
JM
Vazquez
M
M
Gonzalez
F J
FJ
Wahli
W
W
D000222:Adaptation, Physiological; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010957:Plasmids; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D005227:Fatty Acids; D018836:Inflammation Mediators; D008024:Ligands; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D007975:Leukotriene B4; D016718:Arachidonic Acid; C006253:pirinixic acid; D015500:Chloramphenicol O-Acetyltransferase