Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain.

Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Research Abstract Details 

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Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Abstract Text:

Hiroaki Mori,Takashi Nose,Kouki Ishitani,Satoshi Kasagi,Sanae Souma,Taeko Akiyoshi,Yuzo Kodama,Takanori Mori,Miwa Kondo,Shinichi Sasaki,Akihiko Iwase,Kazuhisa Takahashi,Yoshinosuke Fukuchi,Kuniaki Seyama,

Phosphodiesterase 4 (PDE4) is an intracellular enzyme specifically degrading cAMP, a second messenger exerting inhibitory effects on many inflammatory cells. To investigate whether GPD-1116 (a PDE4 inhibitor) prevents murine lungs from developing cigarette smoke-induced emphysema, the senescence-accelerated mouse (SAM) P1 strain was exposed to either fresh air or cigarette smoke for 8 wk with or without oral administration of GPD-1116. We confirmed the development of smoke-induced emphysema in SAMP1 [air vs. smoke (means +/- SE); the mean linear intercepts (MLI), 52.9 +/- 0.8 vs. 68.4 +/- 4.2 mum, P < 0.05, and destructive index (DI), 4.5% +/- 1.3% vs. 16.0% +/- 0.4%, P < 0.01]. Emphysema was markedly attenuated by GPD-1116 (MLI = 57.0 +/- 1.4 mum, P < 0.05; DI = 8.2% +/- 0.6%, P < 0.01) compared with smoke-exposed SAMP1 without GPD-1116. Smoke-induced apoptosis of lung cells were also reduced by administration of GPD-1116. Matrix metalloproteinase (MMP)-12 activity in bronchoalveolar lavage fluid (BALF) was increased by smoke exposure (air vs. smoke, 4.1 +/- 1.1 vs. 40.5 +/- 16.2 area/mug protein; P < 0.05), but GPD-1116 significantly decreased MMP-12 activity in smoke-exposed mice (5.3 +/- 2.1 area/mug protein). However, VEGF content in lung tissues and BALF decreased after smoke exposure, and the decrease was not markedly restored by oral administration of GPD-1116. Our study suggests that GPD-1116 attenuates smoke-induced emphysema by inhibiting the increase of smoke-induced MMP-12 activity and protecting lung cells from apoptosis, but is not likely to alleviate cigarette smoke-induced decrease of VEGF in SAMP1 lungs.

Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Publishing Authors By Initials

H Mori,T Nose,K Ishitani,S Kasagi,S Souma,T Akiyoshi,Y Kodama,T Mori,M Kondo,S Sasaki,A Iwase,K Takahashi,Y Fukuchi,K Seyama,

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Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Lung cellular and

VOLUME: 294

Page Numbers: L196-204

Journal Abbreviation: Am. J. Physiol. Lung Cell Mol.

ISSN: 1040-0605

DAY: 9

MONTH: 11

YEAR: 2007

Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain.

AFFILIATION: Dept. of Respiratory Medicine, Juntendo Univ., School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. kseyama@med.juntendo.ac.jp).

Country: United States

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MEDLINETA: Am J Physiol Lung Cell Mol Phy

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