Volatile anesthetics differentially affect immunostimulated expression of inducible nitric oxide synthase -: Role of intracellular calcium

被引:44
作者
Tschaikowsky, K
Ritter, J
Schröppel, K
Kühn, M
机构
[1] Univ Erlangen Nurnberg, Dept Anesthesiol, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Dept Immunol & Clin Microbiol, D-91054 Erlangen, Germany
关键词
anesthetics; calcium; gene expression; inducible nitric oxide synthase; transcription factors;
D O I
10.1097/00000542-200004000-00028
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background Nitric oxide released by inducible nitric oxide synthase (iNOS) plays an important role in immune responses and systemic vasodilation in septic shock. Volatile anesthetics have been reported to interfere with signal transduction and gene expression. We studied the effect of volatile anesthetics on activity and expression of iNOS and potential mechanisms of action. Methods: Nitrite release and iNOS expression were determined using the Griess reaction and Western and Northern blot techniques, respectively, in J774 murine macrophages stimulated with lipopolysaccharide and gamma-interferon in the absence and presence of various concentrations (0.25-2.0 minimum alveolar concentration [MAC]) of volatile anesthetics (i.e., halothane, enflurane, isoflurane, desflurane). Furthermore, potential interference of volatile anesthetics with specific signal transduction pathways was investigated. Results: All volatile anesthetics, studied in a time- and dose-dependent manner, suppressed nitrite production and iNOS expression in J774 macrophages stimulated by lipopolysaccharide or gamma-interferon at clinically relevant concentrations. The inhibition was completely antagonized by ionomycin but unaffected by diacylglycerol, phorbol myristate acetate, and C2-ceramide. in contrast, in cells costimulated by lipopolysaccharide plus gamma-interferon, volatile anesthetics significantly increased nitrite production and iNOS expression independent of ionomycin and other mediators studied. Conclusions: Volatile anesthetics strongly reduced the mRNA and protein levels of iNOS and NOS activity after a single stimulation with lipopolysaccharide or gamma-interferon, most Likely by attenuating intracellular calcium increase. Costimulation with lipopolysaccharide plus gamma-interferon, however, results in maximum iNOS expression and activity, which are no longer inhibited but are potentiated by volatile anesthetics by unidentified mechanisms.
引用
收藏
页码:1093 / 1102
页数:10
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