Yamaguchi Y, Fukuhara S, Nagase T, Tomita T, Hitomi S, Kimura S, Kurihara H, Ouchi Y
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
J Biol Chem. 2001 Aug 24;276(34):31510-4. doi: 10.1074/jbc.M104149200. Epub 2001 Jun 14.
Defensins comprise a family of cationic antimicrobial peptides that is characterized by the conserved 6 cysteine residues. They are expressed in the epithelial cells of various organs and are identified as key elements in the host defense system at the mucosal surface. We isolated a novel mouse beta-defensin gene from the bacterial artificial chromosome DNA containing the mouse beta-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse beta-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse beta-defensin-3 and 59% identity with mouse beta-defensin-4. We demonstrated the expression of mBD-6 in skeletal muscle in addition to the esophagus, tongue, and trachea. In animal models of endotoxemia, mBD-6 expression was also induced in the lung. mBD-6 showed potent antimicrobial activity against Escherichia coli and would play an important role in host defense in the esophagus, airways, and skeletal muscle. mBD-6 is the first reported beta-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.
防御素是一类阳离子抗菌肽家族，其特征是具有保守的6个半胱氨酸残基。它们在各种器官的上皮细胞中表达，并被确定为黏膜表面宿主防御系统的关键要素。我们从包含小鼠β-防御素-3基因的细菌人工染色体DNA中分离出一个新的小鼠β-防御素基因。从骨骼肌cDNA中克隆出全长cDNA，并将其命名为小鼠β-防御素-6（mBD-6）。预测的肽保留了6个半胱氨酸基序，与小鼠β-防御素-3的氨基酸序列同一性为59%，与小鼠β-防御素-4的同一性为59%。我们证明了mBD-6除了在食管、舌头和气管中表达外，在骨骼肌中也有表达。在内毒素血症动物模型中，肺中也诱导了mBD-6的表达。mBD-6对大肠杆菌显示出强大的抗菌活性，并且在食管、气道和骨骼肌的宿主防御中发挥重要作用。mBD-6是首个被报道主要在骨骼肌中表达的β-防御素。这种独特的组织特异性提示了该肽家族的一些新的生理作用。
