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.
Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
Yasuhiro
Y
Yamaguchi
Takahide
T
Nagase
Ryosuke
R
Makita
Shigetomo
S
Fukuhara
Tetsuji
T
Tomita
Takashi
T
Tominaga
Hiroki
H
Kurihara
Yasuyoshi
Y
Ouchi
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