IFN-gamma is critical to the control of murine autoimmune encephalomyelitis and regulates both in the periphery and in the target tissue: a possible role for nitric oxide
| Autor: | D O, Willenborg, S A, Fordham, M A, Staykova, I A, Ramshaw, W B, Cowden |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Molecular Sequence Data Down-Regulation Nitric Oxide Synthase Type II CD8-Positive T-Lymphocytes Lymphocyte Activation Nitric Oxide Lymphocyte Depletion Interferon-gamma Mice Animals Ascitic Fluid Amino Acid Sequence Enzyme Inhibitors Cells Cultured Receptors Interferon Mice Knockout Interleukin-10 Myelin-Associated Glycoprotein Organ Specificity Lymphocyte Transfusion Radiation Chimera Female Interleukin-4 Nitric Oxide Synthase Spleen |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(10) |
| ISSN: | 0022-1767 |
| Popis: | NO and IFN-gamma have normally been considered cytotoxic and proinflammatory molecules, respectively, in the setting of the central nervous system inflammatory disease autoimmune encephalomyelitis (EAE). Using mice lacking the ligand binding chain of the IFN-gamma receptor (IFNgammaR-/-), we have previously shown that IFN-gamma is not essential for myelin oligodendrocyte glycoprotein peptide (MOG35-55) induced EAE expression but is in fact essential for its down-regulation. Here we examined the downstream molecular and cellular mechanism(s) of IFN-gamma regulation and demonstrate that neither IL-4 nor IL-10 appear to play a role in down-regulation nor do various lymphoid cell populations. Cells of the macrophage lineage are key to down-regulation as evidenced by the fact that peritoneal exudate cells from IFNgammaR+/+ mice inhibit Ag-driven proliferation of IFNgammaR-/- lymphocytes, whereas IFNgammaR-/- peritoneal exudate cells do not. High levels of reactive nitrogen intermediates are detected in the former cultures but not the latter, and the inhibition of proliferation is reversible with an inhibitor of inducible NO synthase, indicating a key role for NO in down-regulation. Studies with bone marrow chimeras indicate that down-regulation occurs not only systemically but also within the target tissue. These data suggest that IFN-gamma down-regulates EAE by inducing inducible NO synthase and subsequently NO production, both by macrophages in the periphery and, by inference, microglia and astrocytes in the target tissue. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|