Abstract
Nitric oxide (NO), products of activated macrophages, have a great impact on the regulation of cytokine production. The role of NO in non-specific host cells is commonly accepted. On the contrary, its role as an immuno-regulatory molecule is still controversial. In this study, we have investigated the effect of NO on the production of cytokines from murine splenocytes and macrophages. S-nitroso-L-glutathione inhibited the release of both interferone-γ and interleukin-2 produced by Th1 cells and tumor necrosis factor-α and interleukin-1β produced by macrophages, but did not affect the release of interleukin-4 and interleukin-10 produced by Th2 cells. These results suggest that NO exerts a down-regulatory effect on the secretion of cytokines from Th1 cells and macrophages which are implicated in immune response. Thus, NO may have an important role as an immuno-modulatory as well as effector molecule in the immune system.
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Adler, H., Frech, B., Thony, M., Pfister, H., Peterhans, E. and Jungi, T.W., Inducible nitric oxide synthetase in cattle. Differential cytokine regulation of nitric oxide synthetase in bovine and murine macrophage.J. Immunol., 154, 4710–4718 (1995).
Cenci, E., Romani, L., Mencacci, A., Spaccapelo, R., Schlaffella, E., Puccetti, P. and Bistoni, F., Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing ofCandida albicans.Eur. J. Immunol., 23, 1034–1038 (1993).
Cox, G.W., Melillo, G., Chattopadhyay, U., Mullet, D., Furtel, R.H. and Varesio, L., Tumor necrosis factor-α dependent production of reactive nitrogen intermediates mediates IFN-α plus IL-2 induced murine macrophage tumoricidal activity.J. Immunol., 149, 3290–3296 (1992).
Ding, A. H., Nathan, C. F., Graycar, J., Derynck, R., Stuehr, D. J. and Srimal, S., Macrophages deactivating factor and transforming growth factor-β1,-β2 and-β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ.J. Immunol., 145, 940–944 (1990).
John, E. C., Ada, M. K., David, H. M., Ethan, M. S. and Warren, S., Current Protocols in Immunology. Vol. 1, Wiley Interscience, A. 3.5–3.7 (1991).
Kim, Y. M., Talanian, R. V., Li, J. and Billiar, T. R., Nitric oxide prevents IL-1beta and IFN-gamma- inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1bata-converting enzyme).J. Immunol., 161(8), 4122–4128 (1998).
Liew, F. Y., Regulation of lymphocyte function by nitric oxide.Curr. Opin. Immunol., 7, 396–399 (1995).
Marcinkiewicz, J., Grabowska, A. and Chain, B.M., Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages.Eur. J. Immunol., 25, 947–951 (1995).
Marcinkiewicz, J., Grabowska, A and Chain, B.M. Is there a role for nitric oxide in regulation of T cell secretion of IL-2?J. Immunol., 156, 4617–4621 (1996).
Miller, R. A. and Britigan, B. E., The formation and biologic significance of phagocyte-derived oxidants.J. Invest. Med., 43, 39–49 (1995).
Merrymann, P. F. and Coffman, R. L., TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.Annu. Rev. Immunol., 7, 145–173 (1989).
Nathan, C. F. and Xie, Q. W., Regulation of the biosynthesis of nitric oxide.J. Biol. Chem., 269, 13725–13728 (1994).
Rockett, K. A., Awburn, M. M., Cowden, W. B. and Clark, I. A., Killing ofPlasmodium falciparum in vitro by nitric oxide derivatives.Infect. Immunity, 59(9), 3280–3283 (1991).
Rogers, N. E. and Ignarro, L. J., Constitutive nitric oxide synthetase from endothelium is reversibly inhibited by nitric oxide formed from L-arginine.Biochem. Biophys. Res. Commun., 189, 244–249 (1992).
Stuehr, D. J., Cho, H. J., Kwon, N. S., Weise, M. F. and Nathan, C. F., Purification and characterization of the cytokine-induced macrophage nitric oxide synthetase: an FAD- and FMN-containing flavoprotein.Proc. Natl. Acad. Sci. USA, 88, 7773–7777 (1991).
Suh, J. S., Eun, J. S., So, J. N., Seo, J. T. and Jhon, G. J., Phagocytic activity of ethyl alcohol fraction of Deer Antler in murine peritoneal macrophage.Biol. Pharm. Bull., 22(9), 932–935 (1999).
Taub, D. D. and Cox, G. W., Murine Th1 and Th2 cell clones differentially regulate macrophage nitric oxide production.J. Leukoc. Biol., 58, 80–89 (1995).
Taylor-Robinson, A. W., Liew, F. Y., Severn, A., Xu, D., McSorley, S., Garside, P., Padron, J. and Phillips, R. S., Regulation of the immune response by nitric oxide differentially produced by T-helper type-1 and T-helper type-2 cells.Eur. J. Immunol., 24, 980–984 (1994).
Xie, Q. and Nathan, C., The high-output nitric oxide pathway: role and regulation.J. Leukoc. Biol., 56, 576–582 (1994).
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Eun, J.S., Suh, Y.H., Kim, D.K. et al. Regulation of cytokine production by exogenous nitric oxide in murine splenocyte and peritoneal macrophage. Arch Pharm Res 23, 531–534 (2000). https://doi.org/10.1007/BF02976585
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DOI: https://doi.org/10.1007/BF02976585