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新型溶血磷脂酸信号拮抗剂KA-1002减轻牛气管细胞损伤和炎症

KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation.

作者信息

Shin Hee-Su, Kim Miok, Kim Kwang Soo, Min Yong Ki, Lee Chang Hoon

机构信息

Bio and Drug Discovery Division, Center for Information-Based Drug Research, Research Institute of Chemical Technology (KRICT), Daejeon 305-600, Korea.

Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Korea.

出版信息

Animals (Basel). 2020 Feb 13;10(2):295. doi: 10.3390/ani10020295.

Abstract

The industrial livestock environment can cause stress and weakened immunity in cattle, leading to microbial infections which reduce productivity. As such, there is a need for an effective therapeutic agent that can alleviate uncontrolled destructive respiratory inflammation. We found that lysophosphatidic acid (LPA), a potent endogenous stress-induced inflammatory agent, causes respiratory tissue damage and triggers inflammation in bovine bronchial cells. LPA also inflames pulmonary bovine blood vessel cells to produce inflammatory cytokines. These findings strongly suggest that LPA is a highly important endogenous material exacerbating bovine respiratory diseases. We further identified a novel LPA-signaling antagonist, KA-1002, and showed that it alleviated LPA-mediated bovine tracheal cell disruption and inflammation. Therefore, KA-1002 could potentially serve as a novel therapeutic agent to maintain physiologically healthy and balanced conditions in bovine respiratory tracts.

摘要

工业化养殖环境会给牛造成压力并削弱其免疫力,导致微生物感染,从而降低生产力。因此,需要一种有效的治疗剂来缓解不受控制的破坏性呼吸道炎症。我们发现,溶血磷脂酸(LPA)是一种内源性应激诱导的强效炎症介质,可导致呼吸道组织损伤并引发牛支气管细胞炎症。LPA还会使牛肺血管细胞发炎,从而产生炎性细胞因子。这些发现有力地表明,LPA是加剧牛呼吸道疾病的一种非常重要的内源性物质。我们进一步鉴定出一种新型LPA信号拮抗剂KA-1002,并表明它可减轻LPA介导的牛气管细胞破坏和炎症。因此,KA-1002有可能作为一种新型治疗剂,维持牛呼吸道的生理健康和平衡状态。

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