Document Detail


TNF-alpha, PDGF, and TGF-beta(1) expression by primary mouse bronchiolar-alveolar epithelial and mesenchymal cells: tnf-alpha induces TGF-beta(1).
MedLine Citation:
PMID:  11502094     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The bronchiolar-alveolar epithelium (BAE) is a primary target site for inhaled agents that cause lung injury. These cells, consequently, release a broad range of mediators that influence other cell populations, including interstitial lung fibroblasts that are central to the development of interstitial pulmonary fibrosis (IPF). A number of peptide growth factors (GF) have been postulated to be essential in the pathogenesis of IPF. We demonstrate here that primary populations of mouse BAE and mesenchymal cells, maintained in culture, synthesize four potent GF. These are platelet-derived growth factor isoforms (PDGF) A and B, transforming growth factor beta-1 (TGF-beta(1)), and tumor necrosis factor alpha (TNF-alpha). A mouse lung epithelial cell isolation technique pioneered in this laboratory has been used to purify the BAE cells to greater than 85% (80 +/- 5.6% alveolar type II and 9 +/- 2.3% Clara cells) in culture. Northern analysis, RNase protection assay, and immunocytochemistry (ICC) were used to establish mRNA and protein expression of the GF over time in the cultured BAE and mesenchymal cells. We show for the first time in these primary mouse lung cells that treatment of both cell types with TNF-alpha upregulates expression of TGF-beta(1). The four GF are produced by both epithelial and mesenchymal cells but with different temporal patterns. TGF-beta(1) is expressed constitutively by BAE and mesenchymal cells, whereas TNF-alpha expression wanes over time. The findings by ICC were consistent with levels of mRNA expression in both cell types. As genetically defined and altered mouse strains are becoming increasingly valuable for modeling lung disease, studying the gene expression patterns of target cells from these animals in vitro would be useful in sorting out the complex responses by individual cell types of the lung and the interactions among the multitude of mediators that are released during lung cell injury.
Authors:
G S Warshamana; M Corti; A R Brody
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental and molecular pathology     Volume:  71     ISSN:  0014-4800     ISO Abbreviation:  Exp. Mol. Pathol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-14     Completed Date:  2001-10-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370711     Medline TA:  Exp Mol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13-33     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Lung Biology Program, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bronchi / cytology*,  immunology
Cell Culture Techniques / methods
Cell Survival / drug effects
Cells, Cultured
Fibroblasts / cytology,  immunology
Gene Expression Regulation / drug effects,  immunology*
Immunohistochemistry
Kinetics
Male
Mesoderm / cytology,  immunology
Mice
Mice, Inbred C57BL
Organ Specificity
Platelet-Derived Growth Factor / genetics*
Protein Biosynthesis
Pulmonary Alveoli / cytology*,  immunology
RNA, Messenger / genetics
Respiratory Mucosa / cytology,  immunology*
Time Factors
Transcription, Genetic
Transforming Growth Factor beta / genetics*,  pharmacology
Tumor Necrosis Factor-alpha / genetics*,  pharmacology
Grant Support
ID/Acronym/Agency:
NRSA HL09691-01/NR/NINR NIH HHS; R01 ES60766/ES/NIEHS NIH HHS; R01 HL60532/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Platelet-Derived Growth Factor; 0/RNA, Messenger; 0/Transforming Growth Factor beta; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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