INTRODUCTION: Unlike C57 Bl/6 (C57) mice, which develop emphysema without obvious fibrosis after chronic exposure to cigarette smoke (CS), DBA/2 mice develop emphysema associated with overt areas of fibrosis. This picture is similar to that described in man with the “Syndrome of Combined Pulmonary Fibrosis and Emphysema”. Thus, in mice like in men, pulmonary changes following to CS may be different and sustained by distinct pathogenic mechanisms. We analysed differences and similarities characterising the development of the CS−induced lung changes in alpha−1PI deficient C57 and DBA/2 mice, which are particularly sensitive to oxidants. METHODS: Mice were exposed to the smoke of 3 cigarettes / day, 5 days/week. At various times, lungs were analysed by morphology, morphometry, immunohistochemistry and biochemical techniques. RESULTS: At the different times after CS exposure, we found in lungs of C57 mice a decreased expression of the membrane bound receptor for advanced glycation end−products (mRAGE). On the contrary, we did not observed in DBA/2 mice significant changes in the expression of mRAGE. With regard to the soluble form of RAGE (sRAGE), we found after CS exposure a significant decrease of sRAGE in DBA/2 mice and no significant changes in C57 mice. These data indicate that a net balance in favour of mRAGE occurs in DBA/2 mice after CS exposure. CONCLUSIONS: RAGE has been recently implicated in programs responsible for acute and chronic inflammation and in lung fibrosis. RAGE signal may induce NF−kB activation and M−CSF hyper−expression promoting inflammation and macrophages activation via alternate pathway. sRAGE may counteract RAGE signal by acting as a “decoy receptor”. Our results suggest that an imbalance between mRAGE and sRAGE can play an important role in the onset of fibrotic lesions associated to lung emphysema after CS exposure

Fineschi, S., De Cunto, G., Cavarra, E., Lungarella, G. (2009). sRAGE/mRAGE imbalance characterizes the cigarette smoke-induced lung changes in oxidant-sensitive DBA/2 mice. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 179, A4158-A4158.

sRAGE/mRAGE imbalance characterizes the cigarette smoke-induced lung changes in oxidant-sensitive DBA/2 mice

De Cunto, G.;Cavarra, E.;Lungarella, G.
2009-01-01

Abstract

INTRODUCTION: Unlike C57 Bl/6 (C57) mice, which develop emphysema without obvious fibrosis after chronic exposure to cigarette smoke (CS), DBA/2 mice develop emphysema associated with overt areas of fibrosis. This picture is similar to that described in man with the “Syndrome of Combined Pulmonary Fibrosis and Emphysema”. Thus, in mice like in men, pulmonary changes following to CS may be different and sustained by distinct pathogenic mechanisms. We analysed differences and similarities characterising the development of the CS−induced lung changes in alpha−1PI deficient C57 and DBA/2 mice, which are particularly sensitive to oxidants. METHODS: Mice were exposed to the smoke of 3 cigarettes / day, 5 days/week. At various times, lungs were analysed by morphology, morphometry, immunohistochemistry and biochemical techniques. RESULTS: At the different times after CS exposure, we found in lungs of C57 mice a decreased expression of the membrane bound receptor for advanced glycation end−products (mRAGE). On the contrary, we did not observed in DBA/2 mice significant changes in the expression of mRAGE. With regard to the soluble form of RAGE (sRAGE), we found after CS exposure a significant decrease of sRAGE in DBA/2 mice and no significant changes in C57 mice. These data indicate that a net balance in favour of mRAGE occurs in DBA/2 mice after CS exposure. CONCLUSIONS: RAGE has been recently implicated in programs responsible for acute and chronic inflammation and in lung fibrosis. RAGE signal may induce NF−kB activation and M−CSF hyper−expression promoting inflammation and macrophages activation via alternate pathway. sRAGE may counteract RAGE signal by acting as a “decoy receptor”. Our results suggest that an imbalance between mRAGE and sRAGE can play an important role in the onset of fibrotic lesions associated to lung emphysema after CS exposure
2009
Fineschi, S., De Cunto, G., Cavarra, E., Lungarella, G. (2009). sRAGE/mRAGE imbalance characterizes the cigarette smoke-induced lung changes in oxidant-sensitive DBA/2 mice. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 179, A4158-A4158.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/44209
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