Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Toxins / immunology
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Colitis / genetics
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Colitis / immunology*
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Colitis / metabolism
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Cytokines / biosynthesis*
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Cytokines / immunology
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Enterotoxins / immunology
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Female
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GTP-Binding Protein alpha Subunits, Gi-Go / deficiency*
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GTP-Binding Protein alpha Subunits, Gi-Go / immunology
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Interleukin-1 / biosynthesis
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Interleukin-1 / immunology
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Interleukin-10 / biosynthesis
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Interleukin-10 / immunology
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Interleukin-12 / biosynthesis
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Interleukin-12 / immunology
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Interleukin-12 Subunit p40
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Minor Lymphocyte Stimulatory Antigens / immunology
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Protein Subunits / biosynthesis
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Protein Subunits / immunology
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Staphylococcus aureus / immunology
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Statistics, Nonparametric
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Superantigens / immunology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / immunology
Substances
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Bacterial Toxins
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Cytokines
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Enterotoxins
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Interleukin-1
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Interleukin-12 Subunit p40
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Minor Lymphocyte Stimulatory Antigens
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Protein Subunits
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Superantigens
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Tumor Necrosis Factor-alpha
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enterotoxin F, Staphylococcal
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Interleukin-10
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Interleukin-12
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GTP-Binding Protein alpha Subunits, Gi-Go