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A keratan sulfatedisaccharide preventsinflammation and theprogression ofemphysema in murinemodels Congxiao GaoReiko FujinawaTakayuki Yoshida2016 год

A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models
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Аннотация: Emphysema is a typical component of chronic obstructive pulmonary disease (COPD), a progressive and inflammatory airway disease. However, no effective treatment currently exists. Here, we show that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette smoke-exposed mice. To confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3--6]Galβ1-4[SO3--6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and microcomputed tomography analyses revealed that, in the mouse elastase-induced emphysema model, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx, as well as the levels of inflammatory cytokines, tissue-degrading enzymes (matrix metalloproteinases), and myeloperoxidase in bronchoalveolar lavage fluid, suggesting that L4 suppressed inflammation in the lung. L4 consistently blocked the chemotactic migration of neutrophils in vitro. Moreover, in the case of the exacerbation model, L4 inhibited inflammatory cell accumulation to the same extent as that of dexamethasone. Taken together, L4 represents one of the potential glycan-based drugs for the treatment of COPD through its inhibitory action against inflammation.
Год издания: 2016
Авторы: Congxiao Gao, Reiko Fujinawa, Takayuki Yoshida, Manabu Ueno, Fumi Ota, Yasuhiko Kizuka, Tetsuya Hirayama, Hiroaki Korekane, Shinobu Kitazume, Toshitaka Maeno, Kazuaki Ohtsubo, Keiichi Yoshida, Yoshiki Yamaguchi, Bernd Lepenies, Jonas Aretz, Christoph Rademacher, Hiroki Kabata, Ahmed E. Hegab, Peter H. Seeberger, Tomoko Betsuyaku, Kozui Kida, Naoyuki Taniguchi
Издательство: American Physical Society
Источник: AJP Lung Cellular and Molecular Physiology
Ключевые слова: Chronic Obstructive Pulmonary Disease (COPD) Research, Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis, Proteoglycans and glycosaminoglycans research
Другие ссылки: AJP Lung Cellular and Molecular Physiology (PDF)
AJP Lung Cellular and Molecular Physiology (HTML)
PubMed (HTML)