Effects of prostaglandins and cyclic AMP on cytokine production in rat leukocytes.
Prostaglandins E1, prostaglandin E2, 3-oxa-methano-prostaglandin I1 (SM-10906), a stable prostaglandin I2 analog, and dibutyryl cyclic AMP suppressed the production of tumor necrosis factor and interleukin-1 in lipopolysaccharide-stimulated rat pleural resident monocytic cells, whereas they enhanced the production of interleukin-6 and cytokine-induced neutrophil chemoattractant (CINC), a rat interleukin-8-like chemokine, in these cells. SM-10906 also inhibited the in vivo production of tumor necrosis factor and interleukin-1 in pleural exudates, when injected into the rat pleural cavity concomitantly with carrageenin. The cyclic AMP (cAMP) level in the lipopolysaccharide-stimulated resident cells was increased when the cells were incubated in the presence of prostaglandin E1, prostaglandin E2 or SM-10906. Prostaglandin I2 showed only slight effects. The addition of pentoxifylline, a phosphodiesterase inhibitor, to the incubation mixture increased the cAMP level and also enhanced the effect of prostaglandins, indicating that these regulating actions of prostaglandins may be exerted partly through a mechanism involving an increased intracellular cAMP level.
Oh-ishi
S
S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Utsunomiya
I
I
Yamamoto
T
T
Komuro
Y
Y
Hara
Y
Y
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000378:metabolism; D002351:Carrageenan; D002460:Cell Line / Q000187:drug effects; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005079:Excipients; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010120:Oxytocics / Q000494:pharmacology*; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; D016207:Cytokines; D005079:Excipients; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010120:Oxytocics; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; C086699:SM 10906; D003994:Bucladesine; D002351:Carrageenan; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone; D010431:Pentoxifylline