title: Overlapping and distinct roles of GRK5 in TLR2-, and TLR3-induced inflammatory response in vivo.
abstract: G-protein coupled receptor kinase-5 (GRK5) is a recently described NFκB regulator in TLR4 signaling pathway. To determine whether the role of GRK5 is MyD88- or TRIF-dependent, we injected wild type and GRK5 knockout mice with Pam3CSK4 (MyD88-dependent TLR1/2 ligand) and Poly(I:C) (TRIF-dependent TLR3 ligand) and examined the in vivo systemic inflammatory response. Our results demonstrate that GRK5 regulates IL-12p40 and G-CSF via a mechanism that is common to both MyD88 and TRIF. However, GRK5 regulates IL-5 and MCP-1 in a MyD88-dependent but TNFα in a TRIF-dependent manner. Together, our results demonstrate multiple roles of GRK5 in TLR signaling.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Nandakumar
authors.initials: N
authors.lastname: Packiriswamy
authors.forename: Sitaram
authors.initials: S
authors.lastname: Parvataneni
authors.forename: Narayanan
authors.initials: N
authors.lastname: Parameswaran
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018932:Chemokine CCL2; D054774:G-Protein-Coupled Receptor Kinase 5; D016179:Granulocyte Colony-Stimulating Factor; D053762:Interleukin-12 Subunit p40; D015848:Interleukin-5; D008024:Ligands; D055666:Lipopeptides; D053594:Myeloid Differentiation Factor 88; D011070:Poly I-C; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; C491768:Ccl2 protein, mouse; C507780:Myd88 protein, mouse; C508075:Pam(3)CSK(4) peptide; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C517895:Grk5 protein, mouse
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