| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 U700, INSERM, Paris, France; Service de Pneumologie, Assistance Publique-Hopitaux de Paris, Hopital Bichat, Paria, France; UFR medicale Denis Diderot, Universite Paris 7, Paria, France
2 U700, INSERM, Paris, France; Service de Pneumologie, Assistance Publique-Hopitaux de Paris, Hopital Bichat, Paris, France; UFR medicale Denis Diderot, Universite Paris 7, Paris, France
3 Laboratory of oxygen metabolism, University of Buenos Aires, University hospital, Buenos Aires, Argentina
4 U700, INSERM, Paris, France
5 Cell Biology Department, Harvard Medical School, Boston, United States
6 INSERM U408, INSERM, Faculte X. Bichat, Paris, 75018, France; Hopital Bichat, CIC 07, Assistance Publique-Hopitaux de Paris, Paris, France
7 U700, INSERM, Paris, France; Hopital Bichat, Service de Pneumologie, Assistance Publique-Hopitaux de Paris, Paris, France; UFR medicale Denis Diderot, Universite Paris 7, Paria, France
* To whom correspondence should be addressed. E-mail: bruno.crestani{at}bch.aphp.fr.
Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The Keratinocyte Growth Factor (KGF) favourably 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/day 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 MCP-1), CXCL2 (or MIP-2
) and of the adhesion molecules ICAM-1 and VCAM-1, 3) a reduction in MMP-2 and MMP-9 activity at Day 3 and 4) a major reduction in DNA damage detected by 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 pre-treatment protected against elastase-induced pulmonary inflammation, activation of MMPs, alveolar cell DNA damage and subsequent emphysema in mice.
This article has been cited by other articles:
|
|
 |
|
  D. Warburton, L. Perin, R. DeFilippo, S. Bellusci, W. Shi, and B. Driscoll Stem/Progenitor Cells in Lung Development, Injury Repair, and Regeneration Proceedings of the ATS, August 15, 2008; 5(6): 703 - 706. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
