|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2010-1-13
|
|
pubmed:abstractText |
Chronic lung diseases are marked by excessive inflammation and epithelial remodeling. Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secretory protein (CCSP) are characteristically seen in these disease states. We sought to define the impact of Clara cell and CCSP depletion on regulation of the lung inflammatory response. We used chemical and genetic mouse models of Clara cell and CCSP deficiency (CCSP(-/-)) coupled with Pseudomonas aeruginosa LPS elicited inflammation. Exposure of Clara cell-depleted or CCSP(-/-) mice to LPS resulted in augmented inflammation as assessed by polymorphonuclear leukocyte recruitment to the airspace. Gene expression analysis and pathway modeling of the CCSP(-/-) inflammatory response implicated increased TNF-alpha signaling. Consistent with this model was the demonstration of significantly elevated TNF-alpha in airway fluid of LPS-stimulated CCSP(-/-) mice compared with similarly exposed wild-type mice. Increased LPS-elicited TNF-alpha production was also observed in cultured lung macrophages from CCSP(-/-) mice compared with wild-type mice. We demonstrate that macrophages from Clara cell-depleted and CCSP(-/-) mice displayed increased Toll-like receptor 4 surface expression. Our results provide evidence that Clara cells can attenuate inflammation through regulation of macrophage behavior, and suggest that epithelial remodeling leading to reduced Clara cell secretory function is an important factor that increases the intensity of lung inflammation in chronic lung disease.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-10027076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-10379362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-10882713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-10949149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-10956619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11108479,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11179105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11193780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11208645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11278724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11589348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11704549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-11804873,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-12153956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-12388377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-12406855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-12449168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-12847263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-14522537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-15047567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-15138169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-15618193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-15696090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-15912112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16034132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16118461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16166619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16387953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16569776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16585588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-16840363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17008535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17123452,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17211498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17384087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17475880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17526599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17673686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17878331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-17921359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-18488036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-18757308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-2440339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-3435451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-7698333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-7875262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-8572241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-8897914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-8908518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-9162006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-9271300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-9271302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19423773-9700096
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Scgb1a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Uteroglobin
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1535-4989
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
42
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
161-71
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
|
