title: Identification and Biological Characterization of Mouse beta-defensin 14, the orthologue of human beta-defensin 3.
abstract: beta-Defensins are small antimicrobial polypeptides that are mainly expressed by epithelial cells and play an important role in the antimicrobial innate immune response. In addition to the direct microbicidal effects of these polypeptides, it became evident that certain members of the beta-defensin super family have the capacity to promote local innate inflammatory and systemic adaptive immune responses by interacting with the CC-chemokine receptor CCR6. We have identified mouse beta-defensin 14 (mBD14, Defb14) as an orthologue of human beta-defensin 3 (hBD3 or DEFB103). Based on primary structural analysis, mBD14 demonstrates greater (68%) homology to its human orthologue, containing three conserved cystein linkages, characteristic for the beta-defensin super family. mBD14 is expressed in a wide variety of tissues including spleen, colon, and tissues of the upper and lower respiratory tract. Interestingly, we also detected mBD14 expression in immature CD11c+ bone marrow-derived dendritic cells. The expression of mBD14 can be induced by Toll-like receptor agonists such as lipopolysaccharide and poly(I:C) and by pro-inflammatory stimuli e.g. tumor necrosis factor and interferon-gamma. Furthermore, expression of mBD14 seems to be regulated by activation of the intracellular pattern recognition receptor NOD2/CARD15 as revealed by reporter gene analysis. We prepared a recombinant mBD14-Ig fusion protein that retained potent antimicrobial activity against several Escherichia coli strains but not against various Gram-positive Staphylococcus aureus strains. hBD3 and also the newly identified mBD14 were chemotactic for cells expressing the mouse CC-chemokine receptor CCR6. In addition, both hBD3 and mBD14 were chemotactic for freshly isolated mouse resident peritoneal cells. Thus, mBD14, based on structural and functional similarities, appears to be an orthologue of hBD3.
authors.affiliation: Institute of Immunology University of Regensburg, D-93042 Regensburg, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Röhrl
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
authors.forename: Thomas
authors.initials: T
authors.lastname: Hehlgans
mesh_terms: D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli / Q000254:growth & development; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D054399:Receptors, CCR6 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000254:growth & development; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C498126:CCR6 protein, mouse; D007369:Interferon Inducers; D008070:Lipopolysaccharides; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D054399:Receptors, CCR6; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D007371:Interferon-gamma; D011070:Poly I-C