Enhanced pro-inflammatory cytokine production in Galphai2-deficient mice on colitis prone and colitis resistant 129Sv genetic backgrounds.
Mice deficient in G-protein subunit alphai2 develop colitis closely resembling human ulcerative colitis when raised on 129SvEv background. When backcrossing the Galphai2-deficiency into a 129SvJBom genetic background, surprisingly, mice did not develop colitis. In vitro stimulation of splenocytes with formalin-killed Staphylococcus aureus resulted in significantly increased production of interleukin-1beta, tumor necrosis factor, and interleukin-12p40 in Galphai2(-/-) as compared to control mice. The enhanced production of pro-inflammatory cytokines was seen in colitis prone as well as in colitis resistant genetic background. A similar outcome was seen upon stimulation with toxic shock syndrome toxin-1, a T cell superantigen, except that Galphai2(-/-) colitis resistant 129SvJBom splenocytes did not show increased production of IL-12p40 as compared to their controls.
Bjursten
Malin
M
Department of Clinical Immunology, Göteborg University, S-413 46, Gothenburg, Sweden. malin.bjursten@microbio.gu.se
Hultgren
Olof H
OH
Hultgren Hörnquist
Elisabeth
E
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency* / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D021122:Protein Subunits / Q000096:biosynthesis / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018709:Statistics, Nonparametric; D018089:Superantigens / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D016747:Minor Lymphocyte Stimulatory Antigens; D021122:Protein Subunits; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D016753:Interleukin-10; D018664:Interleukin-12; D019206:GTP-Binding Protein alpha Subunits, Gi-Go