Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10941006 | Immunobiology | 2013 | 11 Pages |
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.
Keywords
PBEGRKLipoarabinomannanBCGERKHUVECRKIPPI-3KGPCRARDSTLRG protein-coupled receptor kinaseG protein-coupled receptorsAktChronic obstructive pulmonary diseaseCOPDtoll like receptorepithelial cellsAcute respiratory distress syndromeCytokinesPhosphoinositide 3-kinasesLAMMycobacteriaMEKRaf kinase inhibitor proteinmitogen-activated protein kinase kinaseSerine/threonine protein kinaseextracellular signal-regulated kinaseG protein-coupled receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Gisela HÃ¥kansson, Nataliya Lutay, Märta Andersson, Oskar Hallgren, Gunilla Westergren-Thorsson, Majlis Svensson, Gabriela Godaly,