OBJECTIVE: Chemokine receptors are G-protein coupled receptors (GPCRs) phosphorylated by G-protein receptor kinases (GRKs) after ligand-mediated activation. We hypothesized that GRK subtypes differentially regulate granulocyte chemotaxis and clinical disease expression in the K/BxN model. METHODS: Clinical, histologic, and cytokine responses in GRK6-/-, GRK5-/-, GRK2+/-, and wildtype mice were evaluated using K/BxN serum transfer. Granulocyte chemotaxis was analyzed by transendothelial migration assays. RESULTS: Both GRK6-/- and GRK2+/- mice had increased arthritis disease severity (p<0.001); whereas GRK5-/- was not different from controls. Acute weight loss was enhanced in GRK6-/- and GRK2+/- mice (p<0.001, days 3-10). However, GRK6-/- mice uniquely had more weight loss (>10%), elevated serum IL-6, and enhanced migration toward LTB4 and C5a in vitro. CONCLUSIONS: GRK6 and -2, but not GRK5, are involved in the pathogenesis of acute arthritis in the K/BxN model. In particular, GRK6 may dampen inflammatory responses by regulating granulocyte trafficking toward chemoattractants.
OBJECTIVE: Chemokine receptors are G-protein coupled receptors (GPCRs) phosphorylated by G-protein receptor kinases (GRKs) after ligand-mediated activation. We hypothesized that GRK subtypes differentially regulate granulocyte chemotaxis and clinical disease expression in the K/BxN model. METHODS: Clinical, histologic, and cytokine responses in GRK6-/-, GRK5-/-, GRK2+/-, and wildtype mice were evaluated using K/BxN serum transfer. Granulocyte chemotaxis was analyzed by transendothelial migration assays. RESULTS: Both GRK6-/- and GRK2+/- mice had increased arthritis disease severity (p<0.001); whereas GRK5-/- was not different from controls. Acute weight loss was enhanced in GRK6-/- and GRK2+/- mice (p<0.001, days 3-10). However, GRK6-/-mice uniquely had more weight loss (>10%), elevated serum IL-6, and enhanced migration toward LTB4 and C5a in vitro. CONCLUSIONS:GRK6 and -2, but not GRK5, are involved in the pathogenesis of acute arthritis in the K/BxN model. In particular, GRK6 may dampen inflammatory responses by regulating granulocyte trafficking toward chemoattractants.
Authors: Anne Vroon; Annemieke Kavelaars; Volker Limmroth; Maria Stella Lombardi; Marion U Goebel; Anne-Marie Van Dam; Marc G Caron; Manfred Schedlowski; Cobi J Heijnen Journal: J Immunol Date: 2005-04-01 Impact factor: 5.422
Authors: Zhangguo Chen; Rémi Gaudreau; Christian Le Gouill; Marek Rola-Pleszczynski; Jana Stanková Journal: Mol Pharmacol Date: 2004-09 Impact factor: 4.436
Authors: H Ji; D Gauguier; K Ohmura; A Gonzalez; V Duchatelle; P Danoy; H J Garchon; C Degott; M Lathrop; C Benoist; D Mathis Journal: J Exp Med Date: 2001-08-06 Impact factor: 14.307
Authors: Michael D Steury; Ho Jun Kang; Taehyung Lee; Peter C Lucas; Laura R McCabe; Narayanan Parameswaran Journal: Physiol Genomics Date: 2018-03-23 Impact factor: 3.107
Authors: Patrick M Giguère; Matthew J Billard; Geneviève Laroche; Brian K Buckley; Roman G Timoshchenko; Marcus W McGinnis; Denise Esserman; Oded Foreman; Peng Liu; David P Siderovski; Teresa K Tarrant Journal: Mol Immunol Date: 2012-12-29 Impact factor: 4.407
Authors: Teresa K Tarrant; Matthew J Billard; Roman G Timoshchenko; Marcus W McGinnis; D Stephen Serafin; Oded Foreman; Denise A Esserman; Nelson J Chao; William E Lento; David M Lee; Dhavalkumar Patel; David P Siderovski Journal: J Leukoc Biol Date: 2013-08-09 Impact factor: 4.962