Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: G-protein coupled receptor kinase 5 mediates lipopolysaccharide-induced NFκB activation in primary macrophages and modulates inflammation in vivo in mice.

Authors: Patial, Sonika; Shahi, Shipra; Saini, Yogesh; Lee, Taehyung; Packiriswamy, Nandakumar; Appledorn, Daniel M; Lapres, John J; Amalfitano, Andrea; Parameswaran, Narayanan

Published In J Cell Physiol, (2011 May)

Abstract: G-protein coupled receptor kinase-5 (GRK5) is a serine/threonine kinase discovered for its role in the regulation of G-protein coupled receptor signaling. Recent studies have shown that GRK5 is also an important regulator of signaling pathways stimulated by non-GPCRs. This study was undertaken to determine the physiological role of GRK5 in Toll-like receptor-4-induced inflammatory signaling pathways in vivo and in vitro. Using mice genetically deficient in GRK5 (GRK5(-/-) ) we demonstrate here that GRK5 is an important positive regulator of lipopolysaccharide (LPS, a TLR4 agonist)-induced inflammatory cytokine and chemokine production in vivo. Consistent with this role, LPS-induced neutrophil infiltration in the lungs (assessed by myeloperoxidase activity) was markedly attenuated in the GRK5(-/-) mice compared to the GRK5(+/+) mice. Similar to the in vivo studies, primary macrophages from GRK5(-/-) mice showed attenuated cytokine production in response to LPS. Our results also identify TLR4-induced NFκB pathway in macrophages to be selectively regulated by GRK5. LPS-induced IκBα phosphorylation, NFκB p65 nuclear translocation, and NFκB binding were markedly attenuated in GRK5(-/-) macrophages. Together, our findings demonstrate that GRK5 is a positive regulator of TLR4-induced IκBα-NFκB pathway as well as a key modulator of LPS-induced inflammatory response.

PubMed ID: 20945396 Exiting the NIEHS site

MeSH Terms: Animals; Cells, Cultured; Cytokines/metabolism; Female; G-Protein-Coupled Receptor Kinase 5/deficiency; G-Protein-Coupled Receptor Kinase 5/drug effects*; G-Protein-Coupled Receptor Kinase 5/genetics; G-Protein-Coupled Receptor Kinase 5/metabolism; I-kappa B Proteins/metabolism; Inflammation Mediators/metabolism; Inflammation/chemically induced; Inflammation/enzymology*; Inflammation/immunology; Lipopolysaccharides/pharmacology*; Lung/drug effects*; Lung/enzymology; Lung/immunology; Macrophages, Peritoneal/drug effects*; Macrophages, Peritoneal/enzymology; Macrophages, Peritoneal/immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-KappaB Inhibitor alpha; NF-kappa B/metabolism*; Neutrophil Infiltration/drug effects; Phosphorylation; Signal Transduction/drug effects; Time Factors; Toll-Like Receptor 4/agonists; Toll-Like Receptor 4/metabolism

Back
to Top