Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice.
Defensins comprise a family of cationic antimicrobial peptides that are characterized by the presence of six conserved cysteine residues. We identified two novel human beta-defensin (hBD) isoforms by mining the public human genomic sequences. The predicted peptides conserve the six-cysteine motif identical with hBD-4, termed hBD-5 and hBD-6. We also evaluated the characteristics of the mouse homologs of hBD-5, hBD-6, and HE2beta1, termed mouse beta-defensin (mBD)-12, mBD-11, and mouse EP2e (mEP2e). The mBD-12 synthetic peptide showed salt-dependent antimicrobial activity. We demonstrate the epididymis-specific expression pattern of hBD-5, hBD-6, mBD-11, mBD-12, and mEP2e. In situ hybridization revealed mBD-11, mBD-12, and mEP2e expression in the columnar epithelium of the caput epididymis, contrasting with the predominant expression of mBD-3 in the capsule or septum of the whole epididymis. In addition, the regional specificity of mBD-11, mBD-12, and mEP2e was somewhat overlapping, but not identical, in the caput epididymis, suggesting that specific regulation may work for each member of the beta-defensin family. Our findings indicated that multiple beta-defensin isoforms specifically and cooperatively contribute to the innate immunity of the urogenital system.
Yamaguchi
Yasuhiro
Y
Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
Nagase
Takahide
T
Makita
Ryosuke
R
Fukuhara
Shigetomo
S
Tomita
Tetsuji
T
Tominaga
Takashi
T
Kurihara
Hiroki
H
Ouchi
Yasuyoshi
Y
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D004822:Epididymis / Q000737:chemistry* / Q000276:immunology; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006020:Glycopeptides / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D023083:beta-Defensins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000954:Antigens, Surface; C465593:DEFB105A protein, human; C465592:DEFB106A protein, human; C465594:Defb12 protein, mouse; C465583:Defb5 protein, mouse; D006020:Glycopeptides; D020033:Protein Isoforms; D011994:Recombinant Proteins; C087044:SPAG11A protein, human; C465595:Spag11 protein, mouse; D023083:beta-Defensins