Prednisone increases PGH-synthase 2 in atopic humans in vivo.
We compared the expression of prostaglandin H synthase-2 (PGHS-2, cyclooxygenase) message and protein in alveolar macrophages (AM) and blood monocytes (BM) from 20 atopic subjects (AS) and nine control subjects (CS) at baseline and after 1 to 14 d of oral administration of therapeutic doses of prednisone. At baseline, the amounts of PGHS-2 mRNA in AM and BM varied within a similar range among subjects from each group. PGHS-2 protein was present in AM and BM from most AS, but it was also present in CS. In AS, PGHS-2 mRNA and protein significantly increased after prednisone administration, whereas in CS PGHS-2 message and protein remained undetectable or, if present at baseline, was decreased after prednisone. Ex vivo both atopic and normal monocytes and macrophages exhibited the expected decrease in stimulated PGHS-2 mRNA with glucocorticoids. PGHS-1 expression was not altered by prednisone in either group. The differential regulation of the inducible PGHS isoform by prednisone may be mediated by effects on cytokine production in AS.
Dworski
R T
RT
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
Funk
C D
CD
Oates
J A
JA
Sheller
J R
JR
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D011451:Prostaglandin-Endoperoxide Synthases; D011241:Prednisone