Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN).
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Tarrant, TK; Rampersad, RR; Esserman, D; Rothlein, LR; Liu, P; Premont, RT; Lefkowitz, RJ; Lee, DM; Patel, DD
Published Date
- October 2008
Published In
Volume / Issue
- 129 / 1
Start / End Page
- 115 - 122
PubMed ID
- 18662895
Pubmed Central ID
- PMC2637521
Electronic International Standard Serial Number (EISSN)
- 1521-7035
Digital Object Identifier (DOI)
- 10.1016/j.clim.2008.06.008
Language
- eng
Conference Location
- United States