Eicosanoid synthesis in peripheral blood monocytes: a marker of disease activity in lupus nephritis.
A typical feature of lupus nephritis is glomerular and interstitial leukocyte infiltration. In search of a serological marker of renal disease activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subjects and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) released during 24-hour cultures with selective stimuli/inhibitors. Unstimulated basal PGE2 and TxB2 synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal involvement (World Health Organization [WHO] classes IVb-c) and the six lupus patients without active disease than in the five healthy subjects (TxB2, 2,643+/-198 [standard error], 2,015+/-190, 1,548+/-295 pg/10(6) cells, respectively). Escherichia coli lipopolysaccharide (LPS; 10 microg/mL) potently induced TxB2 or PGE2 synthesis in healthy controls (+255%+/-76% and +611%+/-190%, +688%+/-234% and +3,189%+/-154%; 4 to 24 hours, respectively), an effect abolished by 5 micromol/L of dexamethasone (DEX) or by 5 micromol/L of the protein synthesis inhibitor cycloheximide (CHX). Responses to LPS were reduced in lupus patients without disease activity and reduced even further in those with active nephritis. This may be related to substrate depletion or feedback functional inhibition of the inducible isoform of PGHS. Our assay may prove useful in the early detection of kidney disease activity in lupus erythematosus.
Menè
P
P
Department of Experimental Medicine, University La Sapienza of Rome, Italy.
Pecci
G
G
Cinotti
G A
GA
Pugliese
G
G
Pricci
F
F
Pugliese
F
F
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis* / Q000097:blood; D004926:Escherichia coli; D005246:Feedback; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism; D008181:Lupus Nephritis / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015777:Eicosanoids; D005938:Glucocorticoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D013929:Thromboxane B2; D003907:Dexamethasone; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone