Cyclooxygenase 2 pathway mediates IL-1β regulation of IL-1α, -1β, and IL-6 mRNA levels in Leydig cell progenitors (PDF)
Walch,Laurence; Morris,Patricia L.
Endocrinology 143(9): 3276-3283
Publication date: 2002
Prostanoids are arachidonic acid (AA) metabolites derived fromthe cyclooxygenase (COX1 and COX2 isozymes) pathway and areinvolved in signal transduction pathways activated by distinctILs. Although COX1 is the constitutive isoform of COX, IL-1ßis a potent inducer of COX2 expression in distinct cell types.This study was designed to determine whether cyclooxygenasescould mediate endogenous cytokine regulation in rat progenitorLeydig cells. COX and IL (IL-1, IL-1ß, and IL-6) mRNAswere measured by PCR and real-time PCR analyses, respectively.COX function was assessed using COX activity inhibitors: indomethacin(INDO; COX1 and COX2 inhibitor) and NS-398 (COX2 selective inhibitor).Our data indicate that endogenous progenitor COX1 mRNA levelsare low and are not regulated by IL-1ß. In contrast,COX2 mRNA is induced by IL-1ß at 6, 9, and 24 h. IL-1ßinduction of IL mRNAs was in part significantly impaired inthe presence of INDO or NS-398. Among the prostanoids tested,prostaglandin E (PGE), PGF, and carbaprostacyclin reversedthe INDO inhibition of IL production. PGs alone have no (IL-1and IL-1ß) or a modest (IL-6) effect on IL mRNA levels.PGE, PGF, and PGI measurements show that IL-1ßtreatment significantly increases progenitor Leydig cell productionof these PGs. Taken together, our data demonstrate that thisCOX2 cascade is a regulator of cytokines in Leydig progenitors.
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