Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs.: Doxycycline Prevents SM-Induced Respiratory Lesions
| Autor: | Marie-Pia d'Ortho, Stéphane Galiacy, Laurent Taysse, Séraphin Delamanche, Emmanuelle Planus, Jean-Henri Calvet, Christophe Guignabert |
|---|---|
| Přispěvatelé: | Physiopathologie et Thérapeutiques Respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10, Centre d'Etudes du Bouchet, Délégation Générale pour l'Armement, Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was funded by the DGA and the Institut National de la Sante et de la Recherche Medicale (France). |
| Rok vydání: | 2005 |
| Předmět: |
Male
MESH: Inflammation Gelatinases Physiology MESH: Chemical Warfare Agents Respiratory System [CHIM.THER]Chemical Sciences/Medicinal Chemistry Matrix metalloproteinase [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract chemistry.chemical_compound 0302 clinical medicine vesicant agents Gelatinase MESH: Animals MESH: Gelatinases Chemical Warfare Agents MESH: Doxycycline MESH: Respiratory System Doxycycline 0303 health sciences MESH: Protease Inhibitors Sulfur mustard Anti-Bacterial Agents 3. Good health medicine.anatomical_structure MESH: Epithelial Cells [SDV.TOX]Life Sciences [q-bio]/Toxicology 030220 oncology & carcinogenesis medicine.drug Pulmonary and Respiratory Medicine Guinea Pigs protease inhibitors [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology MESH: Guinea Pigs Microbiology Guinea pig 03 medical and health sciences [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Anti-Bacterial Agents Physiology (medical) Mustard Gas [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] medicine Animals Zymography 030304 developmental biology Inflammation Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 doxycycline blistering agents Epithelial Cells Cell Biology Molecular biology MESH: Male MESH: Mustard Gas MESH: Tissue Inhibitor of Metalloproteinase-2 MESH: Tissue Inhibitor of Metalloproteinase-1 chemistry proteases [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Respiratory tract |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, 2005, 289 (1), pp.L67-74. ⟨10.1152/ajplung.00475.2004⟩ |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00475.2004 |
| Popis: | 9 pages; International audience; Respiratory tract lesions induced by the chemical warfare agent sulfur mustard (SM) are characterized by epithelial damages associated with inflammatory cell infiltration. Here we evaluated the imbalance between gelatinase and tissue inhibitors of metalloproteinases (TIMPs), and we tested pretreatment with the protease inhibitor doxycycline. Guinea pigs were intoxicated intratracheally with SM and evaluated 24 h after exposure. Matrix metalloproteinase (MMP) gelatinase activity of bronchial lavage (BL) fluid from SM-exposed guinea pigs was high compared with controls, as shown by both zymography and biotinylated substrate degradation, whereas TIMP-1 and -2 levels by immunoblotting were similar. Extensive areas of lysis were evidenced by in situ zymography, indicating imbalance between gelatinases and inhibitors towards net proteolytic activity. Doxycycline pretreatment resulted in 1) decreased gelatinase activity (zymography, free gelatinase activity assay, and in situ zymography); 2) decreased inflammation (BL fluid cellularity and protein level); and 3) dramatic decrease in histological epithelial lesions. Our results suggest inadequate levels of TIMP to counteract increased gelatinase activity and further support a role for MMP gelatinases in SM-induced respiratory lesions. They also suggest that doxycycline may hold promise as a therapeutic tool. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|