| http://purl.uniprot.org/citations/22445881 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22445881 | http://www.w3.org/2000/01/rdf-schema#comment | "An orphan G-protein-coupled receptor, T cell death-associated gene 8 (TDAG8) which has been reported to be a proton sensor, inhibits the production of pro-inflammatory cytokines induced by extracellular acidification. Recently, we have found that TDAG8 knockout mice showed significant exacerbation in various immune-mediated inflammation disease models. To elucidate the role of TDAG8, we screened an in-house library to find compounds which have a profile as a TDAG8 agonist using a cyclic adenosine 5'-monophosphate assay. Among the screening hits, we focused on (3-[(2,4-dichlorobenzyl)thio]-1,6-dimethyl-5,6-dihydro-1H-pyridazino[4,5-e][1,3,4]thiadiazin-5-one) (named BTB09089). BTB09089 did not act on other proton sensing G-protein-coupled receptors such as G-protein-coupled receptor 4 (GPR4) nor ovarian cancer G-protein-coupled receptor 1 (OGR1). Moreover, BTB09089 increased cAMP level in the splenocytes from wild-type littermates but not from TDAG8-deficient mice. Thus, BTB09089 was found to be a TDAG8 specific agonist. We then investigated the effects of BTB09089 on T cells and macrophages in vitro. In splenocytes, BTB09089 suppressed the production of IL-2 stimulated with anti-CD3 and anti-CD28 antibodies. In peritoneal exuded macrophages induced by thioglycollate, BTB09089 suppressed the production of TNF-α and IL-6 while it increased that of IL-10 when stimulated with lipopolysaccharide. These effects were observed in cells from wild type mice, but not those from TDAG8 knockout mice. These results indicate that activation of TDAG8 attenuates immune-mediated inflammation by regulating the cytokine production of T cells and macrophages."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ejphar.2012.03.007"xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Oda T."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Fujita Y."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Nagasaki M."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Kuwabara H."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Komai T."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/author | "Onozawa Y."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/name | "Eur J Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/pages | "325-331"xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/title | "Activation of T cell death-associated gene 8 regulates the cytokine production of T cells and macrophages in vitro."xsd:string |
| http://purl.uniprot.org/citations/22445881 | http://purl.uniprot.org/core/volume | "683"xsd:string |
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