title: Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages.
abstract: Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-α, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-α production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: He
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tobo
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakakura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komachi
authors.forename: Naoya
authors.initials: N
authors.lastname: Murata
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Takano
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; C513337:GPR65 protein, mouse; D005938:Glucocorticoids; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000242:Cyclic AMP