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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/L648    most recent 90270.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Kubo, K. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Kubo, K.

Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema

¹First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; ²Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha, Hunan, China; ³Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, Virginia

Submitted 9 April 2008 ; accepted in final form 31 January 2009

Chronic inflammation, imbalance of proteolytic and anti-proteolytic activities, oxidative stress, and apoptosis of lung structural cells contribute to the pathogenesis of COPD. Prostacyclin protects cells against apoptosis, has anti-inflammatory properties, partially prevents cigarette smoke extract (CSE)-induced apoptosis of the pulmonary endothelium, and thus may be relevant in the pathogenesis of emphysema. We determined whether a synthetic stable prostacyclin analog, beraprost sodium (BPS), attenuates the development of CSE-induced emphysema and elucidated the molecular mechanisms involved in its effect. Sprague-Dawley rats were treated with BPS and injected with CSE once a week for 3 wk. We measured the DNA damage of cells, the expression of caspase-3, and the activity of matrix metalloproteinase (MMP)-2 and MMP-9. We also analyzed TNF and IL-1β concentrations and the serum antioxidant activity. BPS prevented the development of CSE-induced emphysema, resulting in significant attenuation in alveolar enlargement and pulmonary parenchymal destruction. BPS inhibited pulmonary apoptosis and induction of MMP-2 and MMP-9 activity. Moreover, the protective effect of BPS was associated with a reduction of the expression of proinflammatory cytokines including TNF and IL-1β and a normalized biological oxidant activity. BPS introduces all these events, probably by activating cAMP signaling through acting specific prostacyclin receptors. In conclusion, BPS protects against the development of CSE-induced emphysema by attenuating apoptosis, inhibiting proteolytic enzyme activity, reducing inflammatory cytokine levels, and augmenting antioxidant activity. BPS may potentially represent a new therapeutic option in the prevention of emphysema in humans in prospect.

apoptosis; inflammation; rat; oxidative stress; matrix metalloproteinase