Prostaglandins prevent inducible nitric oxide synthase protein expression by inhibiting nuclear factor‐κB activation in J774 macrophages
1998; Wiley; Volume: 440; Issue: 1-2 Linguagem: Inglês
10.1016/s0014-5793(98)01407-0
ISSN1873-3468
AutoresFulvio D’Acquisto, Lidia Sautebin, Teresa Iuvone, Massimo Di Rosa, Rosa Carnuccio,
Tópico(s)Peroxisome Proliferator-Activated Receptors
ResumoWe investigated the effect of PGE 2 and iloprost (a prostacyclin analogue) on inducible nitric oxide synthase (iNOS) protein expression and nuclear factor‐κB (NF‐κB) activation in lipopolysaccharide (LPS)‐stimulated J774 macrophages. Incubation of J774 cells with LPS (10 μg/ml) caused an increase of iNOS protein expression which was prevented in a concentration‐dependent fashion by PGE 2 (0.1, 1, 10 μM) and iloprost (0.01, 0.1, 1 μM). Electrophoretic mobility shift assay indicated that both prostanoids blocked the activation of NF‐κB, a transcription factor necessary for NO synthase induction. PGE 2 and iloprost also blocked disappearance of IκB‐α from cytosolic fraction and nuclear translocation of NF‐κB subunits p50 and p65. These results show for the first time that PGE 2 and iloprost down‐regulate iNOS protein expression by inhibiting NF‐κB activation and suggest a negative feed‐back mechanism that may be important for limiting excessive or prolonged NO production in pathological events.
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