Objective    To investigate the effect of calmodulin (CaM) inhibitor on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) in mouse RAW264.7 macrophage cells

and to study the anti-inflammation mechanism of CaM inhibitor.     Methods    An inflammatory response model was established using RAW264.7 cells induced by LPS and/or IFN-γ. CaM inhibitors N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and trifluoperazine (TFP) were used to pre-treat RAW264.7 cells to evaluate the effects of the CaM inhibitors. NO concentration was measured with Griess Reagent Kit. Target protein and mRNA expression was tested by Western blot and RT-PCR.     Results    In RAW264.7 cells induced by LPS or IFN-γ

CaM inhibitors W-7 and TFP significantly blocked NO production (P0.01) and protein and mRNA expression of iNOS (P0.01). In RAW264.7 cells induced by LPS and IFN-γ

W-7 and TFP remarkably prevented IκBα degradation (P0.01) and phospho-IKK and phospho-STAT1 protein expression (P0.01).     Conclusion    CaM inhibitors W-7 and TFP can inhibit LPS/IFN-γ-induced NO production and iNOS protein and mRNA expression in RAW264.7 cells

probably by the mechanism of suppressing IκBα degradation and phospho-IKK and phospho-STAT1 protein expression. The anti-inflammatory effects of CaM inhibitors may be associated with NF-κB and JAK-STAT1 signaling pathways.