1. Keratinocyte growth factor protects against elastase-induced pulmonary emphysema in mice
- Author
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Laurent, Plantier, Sylvain, Marchand-Adam, Valeria G, Antico Arciuch, Valeria G, Antico, Laurent, Boyer, Cécile, De Coster, Joëlle, Marchal, Rafik, Bachoual, Arnaud, Mailleux, Jorge, Boczkowski, and Bruno, Crestani
- Subjects
Pulmonary and Respiratory Medicine ,Male ,Pathology ,medicine.medical_specialty ,Fibroblast Growth Factor 7 ,Physiology ,Chemokine CXCL2 ,Vascular Cell Adhesion Molecule-1 ,Inflammation ,Apoptosis ,Biology ,Alveolar cells ,chemistry.chemical_compound ,Mice ,Physiology (medical) ,medicine ,In Situ Nick-End Labeling ,Animals ,RNA, Messenger ,Receptor, Fibroblast Growth Factor, Type 2 ,Pancreatic elastase ,Cells, Cultured ,Chemokine CCL2 ,TUNEL assay ,medicine.diagnostic_test ,Pancreatic Elastase ,Elastase ,Respiratory disease ,Epithelial Cells ,Cell Biology ,respiratory system ,medicine.disease ,Intercellular Adhesion Molecule-1 ,Mice, Inbred C57BL ,Pulmonary Alveoli ,medicine.anatomical_structure ,Bronchoalveolar lavage ,chemistry ,Pulmonary Emphysema ,Matrix Metalloproteinase 2 ,Keratinocyte growth factor ,medicine.symptom ,Bronchoalveolar Lavage Fluid ,DNA Damage - Abstract
Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The keratinocyte growth factor (KGF) favorably influences alveolar maintenance and repair and possesses anti-inflammatory properties. We aimed to determine whether exogenous KGF prevented or corrected elastase-induced pulmonary emphysema in vivo. Treatment with 5 mg·kg−1·day−1 KGF before elastase instillation prevented pulmonary emphysema. This effect was associated with 1) a sharp reduction in bronchoalveolar lavage fluid total protein and inflammatory cell recruitment, 2) a reduction in the pulmonary expression of the chemokines CCL2 (or monocyte chemoattractant protein-1) and CXCL2 (or macrophage inflammatory protein-2α) and of the adhesion molecules ICAM-1 and VCAM-1, 3) a reduction in matrix metalloproteinase (MMP)-2 and MMP-9 activity at day 3, and 4) a major reduction in DNA damage detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) in alveolar cells at day 7. Treatment with KGF after elastase instillation had no effect on elastase-induced emphysema despite the conserved expression of the KGF receptor in the lungs of elastase-instilled animals as determined by immunohistochemistry. In vitro, KGF abolished the elastase-induced increase in CCL2, CXCL2, and ICAM-1 mRNA in the MLE-12 murine alveolar epithelial cell line. We conclude that KGF pretreatment protected against elastase-induced pulmonary inflammation, activation of MMPs, alveolar cell DNA damage, and subsequent emphysema in mice.
- Published
- 2007