Macrophage elastase (MMP-12): a pro-inflammatory mediator?
Mem. Inst. Oswaldo Cruz
;
100(supl.1): 167-172, Mar. 2005. ilus, graf
Artículo
en Inglés
| LILACS
| ID: lil-402194
RESUMO
As many metalloproteinases (MMPs), macrophage elastase (MMP-12) is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD), have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12) in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Metaloendopeptidasas
/
Mediadores de Inflamación
/
Metaloproteinasas de la Matriz
/
Enfermedad Pulmonar Obstructiva Crónica
/
Pulmón
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
Medicina Tropical
/
Parasitología
Año:
2005
Tipo del documento:
Artículo
País de afiliación:
Francia
Institución/País de afiliación:
Pfizer Global R&D/FR
/
University of Rennes/FR
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