PBI-4425, a novel first-in-class anti-inflammatory/anti-fibrotic compound, reduces pulmonary emphysema and cutaneous hyperplasia in tight-skin (Fbn-1) mouse

2017 ◽  
Author(s):  
Lyne Gagnon ◽  
Brigitte Grouix ◽  
Pierre Laurin ◽  
Marie-Pier Cloutier ◽  
Lilianne Geerts ◽  
...  
Keyword(s):  
Pulmonary Emphysema ◽  
Tight Skin ◽  
Anti Inflammatory

Anti-oxidant and anti-inflammatory therapy in hypocomplementemic urticarial vasculitis with pulmonary emphysema

2007 ◽  
Vol 3 (3) ◽  
pp. 147-151 ◽  
Author(s):  
A.V. Kristen ◽  
M.M. Borst ◽  
K. Andrassy ◽  
M. Kirschfink ◽  
J. Müller-Quernheim ◽  
...  
Keyword(s):  
Pulmonary Emphysema ◽  
Urticarial Vasculitis ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Hypocomplementemic Urticarial Vasculitis

Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema

2010 ◽  
Vol 299 (2) ◽  
pp. L184-L191 ◽  
Author(s):  
Gu Seob Roh ◽  
Chin-ok Yi ◽  
Yu Ji Cho ◽  
Byeong Tak Jeon ◽  
Irina Tsoy Nizamudtinova ◽  
...  
Keyword(s):  
Pulmonary Emphysema ◽  
Pulmonary Inflammation ◽  
Inhibitory Effect ◽  
No Production ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Rat Lungs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Regulated Gene Expression

Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drug's anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we explore whether celecoxib attenuates CS-induced inflammation in rat lungs. Rats were exposed to smoke and received celecoxib via intragastric feeding daily for 20 wk. We found that celecoxib inhibited interalveolar wall distance and pulmonary inflammation in the lungs of CS-treated rats. Celecoxib inhibited serum NO production, iNOS, COX-2 expression, and PGE2 production in CS-treated lung tissues. Our immunohistochemical data showed that CS-induced CD68 and COX-2 expression were inhibited by celecoxib. Furthermore, celecoxib attenuated the activation of phospho-IκBα and NF-κB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-κB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-κB activation in COX-2 siRNA-transfected RAW 264.7 macrophages. Thus, our findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-κB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.

scholarly journals Reversal of elastase-induced pulmonary emphysema and promotion of alveolar epithelial cell proliferation by simvastatin in mice

2008 ◽  
Vol 294 (5) ◽  
pp. L882-L890 ◽  
Author(s):  
Saeko Takahashi ◽  
Hidetoshi Nakamura ◽  
Makoto Seki ◽  
Yoshiki Shiraishi ◽  
Miyuki Yamamoto ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Pulmonary Emphysema ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Morphometric Parameter ◽  
Endothelial Cell Function ◽  
Alveolar Epithelial ◽  
Anti Inflammatory

Besides lowering cholesterol, statins exert multiple effects, such as anti-inflammatory activity and improvement of endothelial cell function. We examined whether simvastatin (SS) protects against the development of elastase-induced pulmonary emphysema in mice by using mean linear intercepts of alveoli (Lm) as a morphometric parameter of emphysema. After injection of intratracheal elastase on day 0, C57BL/6 mice were treated daily with SS (SS+ group) or PBS (SS− group) for 2 wk. A 21% decrease in Lm on day 7 was observed in the SS+ group vs. the SS− group. Anti-inflammatory effects of SS were observed as a decrease in percentage of neutrophils up to day 3, and in hydroxyproline concentration on day 3, in bronchoalveolar lavage fluid (BALF). SS also increased the number of proliferating cell nuclear antigen (PCNA)-positive alveolar epithelial cells between days 3 and 14. To confirm the role of statins in promoting proliferation of alveolar cells, mice were treated with SS (SS+) vs. PBS (SS−) for 12 days, starting 3 wk after elastase administration. After SS treatment, Lm decreased by 52% and PCNA-positive alveolar epithelial cells increased compared with the SS− group. Concentrations of vascular endothelial growth factor in BALF and endothelial nitric oxide synthase protein expression in pulmonary vessels tended to be higher in the SS+ group vs. the SS− group in this protocol. In conclusion, SS inhibited the development of elastase-induced pulmonary emphysema in mice. This therapeutic effect was due not only to anti-inflammation but also to the promotion of alveolar epithelial cell regeneration, partly mediated by restoring endothelial cell functions.

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