A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models

作者：Gao Congxiao; Fujinawa Reiko; Yoshida Takayuki; Ueno Manabu; Ota Fumi; Kizuka Yasuhiko; Hirayama Tetsuya; Korekane Hiroaki; Kitazume Shinobu; Maeno Toshitaka; Ohtsubo Kazuaki; Yoshida Keiichi; Yamaguchi Yoshiki; Lepenies Bernd; Aretz Jonas; Rademacher Christoph; Kabata Hiroki; Hegab Ahmed E; Seeberger Peter H; Betsuyaku Tomoko; Kida Kozui; Taniguchi Naoyuki^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017, 312(2): L268-L276.

DOI：10.1152/ajplung.00151.2016

• chronic obstructive pulmonary disease
• glycan
• keratan sulfate
• L4

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 (GAGs) produced in the small airway, decreased in lungs of cigarette-smoke-exposed mice. In order to confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3--6]Gal beta 1-4[SO3--6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and micro-computed tomography (micro-CT) analyses revealed that, in the elastase-induced emphysema model mice, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx and the levels of inflammatory cytokines, tissue-degrading enzymes (MMPs), and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) 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.

• 出版日期2017-2
• 单位RIKEN