Document Detail

Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury.
MedLine Citation:
PMID:  18065658     Owner:  NLM     Status:  MEDLINE    
The mechanisms of pulmonary repair in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are poorly known. Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are key factors involved in alveolar epithelial repair, present in the bronchoalveolar lavage fluid (BALF) from patients with ALI/ARDS. The role of BALF mediators in their production remains to be determined. We evaluated the overall effect of BALF from 52 patients (27 ventilated patients with ALI/ARDS, 10 ventilated patients without ALI, and 15 nonventilated control patients) on HGF and KGF synthesis by lung fibroblasts. Fibroblasts were cultured in the presence of BALF. HGF and KGF protein secretion was measured using ELISA, and mRNA expression was evaluated using quantitative real-time RT-PCR. Only BALF from ALI/ARDS patients upregulated both HGF and KGF mRNA expression and protein synthesis (+271 and +146% for HGF and KGF, respectively). BALF-induced HGF synthesis from ALI/ARDS patients was higher than that from ventilated patients without ALI (P < 0.05). HGF secretion was correlated with BALF IL-1beta levels (rho = 0.62, P < 0.001) and BALF IL-1beta/IL-1 receptor antagonist ratio (rho = 0.54, P < 0.007) in the ALI/ARDS group. An anti-IL-1beta antibody partially (>50%) inhibited the BALF-induced HGF and PGE(2) secretion, whereas NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, completely inhibited it. Anti-IL-1beta antibodies as well as NS-398 reversed the COX-2 upregulation induced by BALF. Therefore, IL-1beta is a main BALF mediator involved in HGF secretion, which is mediated through a PGE(2)/COX-2-dependent mechanism. BALF mediators may participate in vivo in the production of HGF and KGF by lung fibroblasts during ALI/ARDS.
Christophe Quesnel; Sylvain Marchand-Adam; Aurélie Fabre; Joëlle Marchal-Somme; Ivan Philip; Sigismond Lasocki; Véronique Leçon; Bruno Crestani; Monique Dehoux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-07
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  294     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-12     Completed Date:  2008-03-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L334-43     Citation Subset:  IM    
Laboratoire de Biochimie A, Hôpital Bichat, AP-HP, 46 rue Henri Huchard, 75018 Paris, France.
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MeSH Terms
Antibodies / pharmacology
Bronchoalveolar Lavage Fluid / cytology
Cell Line
Cyclooxygenase 2 / genetics,  metabolism
Cyclooxygenase 2 Inhibitors / pharmacology
Dinoprostone / metabolism
Fibroblast Growth Factor 7 / genetics,  secretion
Fibroblasts / drug effects,  enzymology,  secretion*
Gene Expression Regulation / drug effects
Hepatocyte Growth Factor / genetics,  secretion*
Interleukin 1 Receptor Antagonist Protein / metabolism
Interleukin-1beta / metabolism
Middle Aged
RNA, Messenger / genetics,  metabolism
Respiratory Distress Syndrome, Adult / enzymology,  metabolism*,  pathology*
Reg. No./Substance:
0/Antibodies; 0/Cyclooxygenase 2 Inhibitors; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1beta; 0/RNA, Messenger; 126469-10-1/Fibroblast Growth Factor 7; 363-24-6/Dinoprostone; 67256-21-7/Hepatocyte Growth Factor; EC 2

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

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