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GPCR kinase‐6 inhibits neutrophil infiltration but mediates bacterial killing during lung bacterial infection (145.5)
Author(s) -
Parameswaran Narayanan,
Packiriswamy Nandakumar,
Lee Taehyung
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.145.5
Subject(s) - g protein coupled receptor kinase , g protein coupled receptor , kinase , lung , inflammation , infiltration (hvac) , receptor , biology , serine , signal transduction , beta adrenergic receptor kinase , microbiology and biotechnology , immunology , phosphorylation , medicine , biochemistry , physics , thermodynamics
GPCR kinases (GRKs) are serine/threonine kinases known to be critical players in desensitization of GPCRs. Recent studies have implicated GRKs in a number of different physiological and pathophysiological processes including biased signaling from GPCRs as well as signaling from receptors other than non‐GPCRs. In this study we examined the role of GRK6 (one of the seven GRKs) in E. Coli‐induced lung infection and inflammation model using wild type and GRK6 deficient mice. Intra‐tracheal instillation of E. Coli led to enhanced infiltration of neutrophils into lung tissue of GRK6 deficient mice compared to wild type mice. Enhanced neutrophil infiltration was associated with enhanced IL‐17 expression in the GRK6 deficient lung following infection. Interestingly, even though there was increased neutrophil infiltration, the bacterial persistence and the subsequent mortality were significantly higher in the GRK6 deficient mice. Intriguingly our studies also reveal that GRK6 deficient neutrophils are inefficient in bacterial killing, suggesting that the observed phenotype of increased bacterial load and mortality is likely due to defective bacterial clearance by GRK6 deficient neutrophils. Our studies reveal a previously unrecognized and novel role of GRK6 in bacterial clearance in lung infection model. Grant Funding Source : Supported by NIH