Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-8
pubmed:abstractText
Altered airway smooth muscle (ASM) function and enrichment of the extracellular matrix (ECM) with interstitial collagen and fibronectin are major pathological features of airway remodeling in asthma. We have previously shown that these ECM components confer enhanced ASM proliferation in vitro, but their action on its newly characterized secretory function is unknown. Here, we examined the effects of fibronectin and collagen types I, III, and V on IL-1beta-dependent secretory responses of human ASM cells, and characterized the involvement of specific integrins. Cytokine production (eotaxin, RANTES, and GM-CSF) was evaluated by ELISA, RT-PCR, and flow cytometry. Function-blocking integrin mAbs and RGD (Arg-Gly-Asp)-blocking peptides were used to identify integrin involvement. IL-1beta-dependent release of eotaxin, RANTES, and GM-CSF was enhanced by fibronectin and by fibrillar and monomeric type I collagen, with similar changes in mRNA abundance. Collagen types III and V had no effect on eotaxin or RANTES release but did modulate GM-CSF. Analogous changes in intracellular cytokine accumulation were found, but in <25% of the total ASM cell population. Function-blocking Ab and RGD peptide studies revealed that alpha2beta1, alpha5beta1, alphavbeta1, and alphavbeta3 integrins were required for up-regulation of IL-1beta-dependent ASM secretory responses by fibronectin, while alpha2beta1 was an important transducer for type I collagen. Thus, fibronectin and type I collagen enhance IL-1beta-dependent ASM secretory responses through a beta1 integrin-dependent mechanism. Enhancement of cytokine release from ASM by these ECM components may contribute to airway wall inflammation and remodeling in asthma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Blocking, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29, http://linkedlifedata.com/resource/pubmed/chemical/CCL11 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL11, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2258-64
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15699160-Adjuvants, Immunologic, pubmed-meshheading:15699160-Adult, pubmed-meshheading:15699160-Aged, pubmed-meshheading:15699160-Antibodies, Blocking, pubmed-meshheading:15699160-Antibodies, Monoclonal, pubmed-meshheading:15699160-Antigens, CD29, pubmed-meshheading:15699160-Cells, Cultured, pubmed-meshheading:15699160-Chemokine CCL11, pubmed-meshheading:15699160-Chemokines, CC, pubmed-meshheading:15699160-Collagen Type I, pubmed-meshheading:15699160-Cytokines, pubmed-meshheading:15699160-Extracellular Matrix Proteins, pubmed-meshheading:15699160-Female, pubmed-meshheading:15699160-Fibronectins, pubmed-meshheading:15699160-Gene Expression Regulation, pubmed-meshheading:15699160-Humans, pubmed-meshheading:15699160-Interleukin-1, pubmed-meshheading:15699160-Intracellular Fluid, pubmed-meshheading:15699160-Lung, pubmed-meshheading:15699160-Male, pubmed-meshheading:15699160-Middle Aged, pubmed-meshheading:15699160-Muscle, Smooth
pubmed:year
2005
pubmed:articleTitle
Multiple beta 1 integrins mediate enhancement of human airway smooth muscle cytokine secretion by fibronectin and type I collagen.
pubmed:affiliation
Department of Asthma, Allergy and Respiratory Science, The Guy's, King's and St. Thomas' School of Medicine, King's College London, Guy's Hospital Campus, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't