title: Epithelial G protein-coupled receptor kinases regulate the initial inflammatory response during mycobacterial infection.
abstract: The interaction between mycobacteria and epithelium is unexplored, but may determine the outcome of the infection. We have analyzed the role of two G protein-coupled receptors, CXCR1 and CXCR2 that are important regulators of many pulmonary diseases. We found that mycobacteria significantly increased the expression of both CXCR1 and CXCR2 on alveolar epithelial cells and both receptors were found to be important for neutrophil diapedesis across primary endothelial cells towards infected mucosa. Mycobacteria, lipoarabinomannan or 19-kDa glycolipoprotein up-regulated the inhibitory G protein-coupled receptor kinase (GRK)2, while GRK3 was less affected. Mycobacteria-induced GRK2 up-regulation decreased chemokine transcription and secretion thereby affecting the neutrophil recruitment to infected mucosa. These events were completely abolished by blocking these receptors prior to infection as the blocking increased epithelial immune responses. We have identified novel interactions occurring in the initial phase of mycobacterial infections by which mycobacterial manipulate epithelial inflammatory responses.
authors: Department of MIG, Division of Laboratory Medicine, Lund University, Lund, Sweden.
authors: Gisela
authors: G
authors: Håkansson
authors: Nataliya
authors: N
authors: Lutay
authors: Märta
authors: M
authors: Andersson
authors: Oskar
authors: O
authors: Hallgren
authors: Gunilla
authors: G
authors: Westergren-Thorsson
authors: Majlis
authors: M
authors: Svensson
authors: Gabriela
authors: G
authors: Godaly
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000276:immunology*; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C050016:lipoarabinomannan; D054770:G-Protein-Coupled Receptor Kinase 3; C496567:GRK2 protein, human; C517848:GRK3 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2