The specific type IV phosphodiesterase inhibitor rolipram differentially regulates the proinflammatory mediators TNF-alpha and nitric oxide.
We compared the effect of the specific type IV phosphodiesterase inhibitor rolipram on intracellular cAMP concentration, nitric oxide (NO) and tumour necrosis factor-alpha (TNF) formation in the murine macrophage cell line RAW 264.7. We found a dose-dependent increase of nitrite accumulation in LPS-stimulated macrophages from 17.5 to 25.1 microM nitrite with rolipram, whereas TNF synthesis was suppressed to less than 30% of control. This was accompanied by an increase from 7.4 to a maximum of 10.5 nM cAMP in RAW cells incubated with rolipram. These results were confirmed with the stable cAMP analogue (S)-p-adenosine 3',5'-cyclic phosphorothioate [(S)-p-cAMPS]. These findings demonstrate that elevation of cAMP in RAW 264.7 cells by rolipram decreases TNF synthesis and increases NO formation.
Greten
T F
TF
Medizinische Klinik, Klinikum Innenstadt Ludwig-Maximilians-Universitt, München, Germany.
Eigler
A
A
Sinha
B
B
Moeller
J
J
Endres
S
S
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009573:Nitrites; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000242:Cyclic AMP; D020889:Rolipram