Rig-I-/- mice develop colitis associated with downregulation of G alpha i2
| Autor: | Shunyuan Lu, Xue-Song Liu, Yi Wang, Wei Dai, Hong-Xin Zhang, Hui Kong, Zhu Chen, Xi-Hua Li, Qiao-Ling Liu, Long Wang, Zi-Xing Liu, Yue-Ping Sun, Sai-Juan Chen, Zhen-Yu Lu, Zhugang Wang, Shisan Bao |
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| Rok vydání: | 2007 |
| Předmět: |
G protein
medicine.drug_class viruses T-Lymphocytes Mutant Blotting Western Alpha (ethology) chemical and pharmacologic phenomena Apoptosis Biology DEAD-box RNA Helicases Mice Downregulation and upregulation medicine Animals Retinoid Receptor Molecular Biology Cells Cultured Mice Knockout RIG-I Reverse Transcriptase Polymerase Chain Reaction Dextran Sulfate virus diseases Cell Biology biochemical phenomena metabolism and nutrition Type I interferon production Blotting Northern Colitis Molecular biology NIH 3T3 Cells DEAD Box Protein 58 biological phenomena cell phenomena and immunity GTP-Binding Protein alpha Subunit Gi2 |
| Zdroj: | Cell research. 17(10) |
| ISSN: | 1748-7838 |
| Popis: | RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I(-/-) mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I(-/-) mice are viable and fertile. Histological analysis shows that Rig-I(-/-) mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein alpha i2 subunit (G alpha i2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated G alpha i2 expression. Moreover, G alpha i2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis. |
| Databáze: | OpenAIRE |
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