Cyclooxygenase-1 mediates the immediate corticosterone response to peripheral immune challenge induced by lipopolysaccharide.
Immune-induced activation of the hypothalamus-pituitary-adrenal axis is mediated by cyclooxygenase derived prostaglandins. Here we examined the role of cyclooxygenase-1 in this response, by using genetically modified mice as well as pharmacological inhibition. We found that mice with a deletion of the gene encoding cyclooxygenase-1, in contrast to wild type mice, did not show increased plasma corticosterone at 1h after immune challenge by peripheral injection of bacterial wall lipopolysaccharide, whereas the corticosterone levels were similarly elevated in both genotypes at 6h post-injection. Pretreatment of mice with the selective cyclooxygenase-1 inhibitor SC-560, given orally, likewise inhibited the rapid corticosterone response. These findings, taken together with our recent demonstration that the delayed stress hormone response to immune challenge is dependent on cyclooxygenase-2, show that the two cyclooxygenase isoforms play distinct, but temporally supplementary roles for the stress hormone response to inflammation.
Elander
Louise
L
Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden.
Ruud
Johan
J
Korotkova
Marina
M
Jakobsson
Per-Johan
PJ
Blomqvist
Anders
A
D000284:Administration, Oral; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011720:Pyrazoles; C115461:SC 560; D051545:Cyclooxygenase 1; D003345:Corticosterone