Cerebral gene expression of superantigen encephalitis in the lewis rat induced by staphylococcal enterotoxin a.
Superantigens were suggested to play a role in the pathogenesis of different autoimmune diseases including multiple sclerosis (MS). Previously, it was demonstrated that local expression of the superantigen, staphylococcal enterotoxin A (SEA) in the brain of rats may lead to encephalitis which was amplified by using intravenous injection of concanavalin A (ConA)-activated splenocytes. In the present investigation, gene expression was studied in the rat brain 8 days after an injection of 50 mul of 1 mg/ml SEA or saline and 5 days after an intravenous injection of 1 x 10(7) ConA-activated spleen cells. Of 8800 genes investigated (Affymetrix, rat genome U34A), the expression of 106 genes was significantly and at least threefold increased with SEA, while the expression of 29 genes was decreased at least threefold. Increased gene expression was compatible with an intracerebral inflammatory response mediated by antigen-presenting cells and CD8+ T lymphocytes. Elevated chemokines comprised RANTES (CCL5), osteopontin, MCP-1 (CCL2) and CXCL10. Further, genes with increased expression were assigned to the extracellular matrix, microglia/macrophage cell elements, astrocytes (GFAP) and phagocytosis. There was considerable conformity between previously reported gene expression profiles for experimental autoimmune encephalomyelitis (EAE) or MS and the present findings. Our data are in line with the concept that T-cell superantigen locally expressed in the central nervous system induces an inflammatory response. Therefore, the study of gene expression profiles does not seem to allow clear conclusions with respect to the aetiology of central nervous system autoimmune diseases.
Emmer
A
A
Department of Neurology, Martin-Luther-Universität-Halle-Wittenberg, Halle, Germany.
Gerlach
K
K
Staege
M S
MS
Kornhuber
M E
ME
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D004660:Encephalitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004768:Enterotoxins / Q000009:adverse effects / Q000276:immunology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D018089:Superantigens / Q000235:genetics*
D018925:Chemokines; D004768:Enterotoxins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal