TAILIEUCHUNG - Báo cáo khoa học: A pathway through interferon-c is the main pathway for induction of nitric oxide upon stimulation with bacterial lipopolysaccharide in mouse peritoneal cells

Production of nitric oxide (NO) in response to bacterial lipopolysaccharide (LPS) was investigated using cultures of mouse peritoneal exudate cells (PEC) and the macrophage cell line . In the presence of anti-(interferon-c) (IFN-c), NO production was markedly suppressed in the PEC culture but not in the culture. In the PEC culture, LPS induced both IFN-cproduction and activation of IFNresponse factor-1, which leads to the gene expression of inducible NO synthase, but neither was induced in the culture of cells | Eur. J. Biochem. 270 4016-4025 2003 FEBS 2003 doi A pathway through interferon-c is the main pathway for induction of nitric oxide upon stimulation with bacterial lipopolysaccharide in mouse peritoneal cells Motohiro Matsuura1 Shinji Saito1 Yoshikazu Hirai1 and Haruki Okamura2 1 Department of Microbiology Jichi Medical School Tochigi Japan 2Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo Japan Production of nitric oxide NO in response to bacterial lipopolysaccharide LPS was investigated using cultures of mouse peritoneal exudate cells PEC and the macrophage cell line . In the presence of anti- interferon-y IFN-y NO production was markedly suppressed in the PEC culture but not in the culture. In the PEC culture LPS induced both IFN-y production and activation of IFN response factor-1 which leads to the gene expression of inducible NO synthase but neither was induced in the culture of cells. In addition to anti- IFN-y antibodies against interleukin IL -12 and IL-18 showed a suppressive effect on LPS-induced NO production in the PEC culture and these antibodies in synergy showed strong suppression. Stimulation of the PEC culture with IL-12 or IL-18 induced production of IFN-y and NO and these cytokines in combination exhibited marked synergism. Stimulation of the culture with IFN-y induced production of NO but not IL-12. The macrophage population in the PEC prepared as adherent cells responded well to LPS for IL-12 production but weakly for production of IFN-y and NO. The macrophages also responded well to IFN-y for NO production. For production of IFN-y by stimulation with LPS or IL-12 IL-18 nonadherent cells were required in the PEC culture. Considering these results overall the indirect pathway through the production of intermediates such as IFN-y-inducing cytokines and IFN-y by the cooperation of macrophages with nonadherent cells was revealed to play the main role in .

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