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Epithelial G protein-coupled receptor kinases regulate the initial inflammatory response during mycobacterial infection.

Håkansson, Gisela LU ; Lutay, Nataliya LU ; Andersson, Märta LU ; Hallgren, Oskar LU ; Westergren-Thorsson, Gunilla LU orcid ; Svensson, Majlis LU and Godaly, Gabriela LU orcid (2013) In Immunobiology 218(7). p.984-994
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... (More)
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunobiology
volume
218
issue
7
pages
984 - 994
publisher
Elsevier
external identifiers
  • wos:000320485300007
  • pmid:23312955
  • scopus:84877141728
  • pmid:23312955
ISSN
1878-3279
DOI
10.1016/j.imbio.2012.11.001
language
English
LU publication?
yes
id
29c9581f-d903-4c78-a9fb-342992c1763f (old id 3438783)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23312955?dopt=Abstract
date added to LUP
2016-04-01 10:35:25
date last changed
2024-04-07 13:35:13
@article{29c9581f-d903-4c78-a9fb-342992c1763f,
  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.}},
  author       = {{Håkansson, Gisela and Lutay, Nataliya and Andersson, Märta and Hallgren, Oskar and Westergren-Thorsson, Gunilla and Svensson, Majlis and Godaly, Gabriela}},
  issn         = {{1878-3279}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{984--994}},
  publisher    = {{Elsevier}},
  series       = {{Immunobiology}},
  title        = {{Epithelial G protein-coupled receptor kinases regulate the initial inflammatory response during mycobacterial infection.}},
  url          = {{http://dx.doi.org/10.1016/j.imbio.2012.11.001}},
  doi          = {{10.1016/j.imbio.2012.11.001}},
  volume       = {{218}},
  year         = {{2013}},
}