The induction of cyclooxygenase-2 (COX-2) in intact human amnion tissue by interleukin-4.
Infection is a major cause of preterm labor. Amniotic fluid from women in preterm labor associated with intrauterine infection contains increased concentrations of cytokines. The mechanism underlying this association may be a cytokine-mediated stimulation of amnion cell prostaglandin production. The biosynthesis of prostaglandins from arachidonic acid is regulated by the enzyme cyclooxygenase which exists in two forms; the constitutive form (COX-1) and the other mitogen inducible (COX-2). The purpose of this study was to evaluate the effect of the cytokine interleukin-4 (IL-4) on cyclooxygenase activity and PGE2 production in amnion. Amnion tissue was taken at caesarean section from term women not in labor and immediately incubated for 2 hours in media containing concentrations of IL-4 ranging from 1 to 100 ng/ml. An increase in both COX-2 enzyme and prostaglandin E2 (PGE2) production was observed for all concentrations of IL-4 greater than 25 ng/ml (P < 0.05, n = 8). No change in COX-1 was observed. Our data suggest that the cytokine IL-4 may be involved in the pathogenesis of premature labor by inducing COX-2 in amnion tissue resulting in increased production of PGE2 and subsequent myometrial activity.
Spaziani
E P
EP
University of South Florida Health Science Center, Department of OB/GYN, Tampa 33612, USA.
Lantz
M E
ME
Benoit
R R
RR
O'Brien
W F
WF
D000650:Amnion / Q000187:drug effects* / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D003124:Colorimetry / Q000379:methods; D004396:Coloring Agents; D046508:Culture Techniques; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D007752:Obstetric Labor, Premature / Q000201:enzymology*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D015847:Interleukin-4; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C022616:thiazolyl blue; D015232:Dinoprostone