Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P81534 (hBD-3)
 230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification and Biological Characterization of Mouse beta-defensin 14, the orthologue of human beta-defensin 3. 1816 48

Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number of important cellular processes and have been suggested to have roles in regulating membrane traffic. Given the proposed role of septins in cell membrane dynamics, we investigated the function of septins during FcgammaR-mediated phagocytosis. We show that several septins are expressed in RAW264.7 and J774 mouse macrophage cell lines and that SEPT2 and SEPT11 are colocalized with submembranous actin-rich structures during the early stages of FcgammaR-mediated phagocytosis. In addition, SEPT2 accumulation is seen in primary human neutrophils and in nonprofessional phagocytes. The time course of septin accumulation mirrors actin accumulation and is inhibited by latrunculin and genistein, but not other inhibitors of phagocytosis. Inhibition of septin function by transient expression of the BD3 domain of BORG3, known to cause septin aggregation, or depletion of SEPT2 or SEPT11 by RNAi, significantly inhibited FcgammaR-mediated phagocytosis of IgG-coated latex beads. Interestingly, this occurred without affecting the accumulation of actin or the actin-associated protein coronin-1. These observations show that, although not necessary for actin recruitment, septins are required for efficient FcgammaR-mediated phagocytosis.
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PMID:Mammalian septins are required for phagosome formation. 1827 90

Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. Antimicrobial human beta-defensins (hBDs) not only exhibit potent bactericidal activities against Gram-negative and Gram-positive bacteria but also function as immunomodulatory molecules by inducing cytokine and chemokine production and inflammatory and immune cell activation. Neutrophil is a critical effector cell in host defense against microbial infection, and its lifespan is regulated by various pathogen- and host-derived substances. Here, to further evaluate the role of hBDs in innate immunity, we investigated the action of hBD-1 to -4 on neutrophil apoptosis. Neutrophil apoptosis was assessed using human blood neutrophils based on the morphological changes. Of note, hBD-3 most potently suppressed neutrophil apoptosis among hBD-1 to -4, accompanied with the down-regulation of truncated Bid (a pro-apoptotic protein), up-regulation of Bcl-x(L) (an anti-apoptotic protein) and inhibition of mitochondrial membrane potential change and caspase 3 activity. Furthermore, we revealed that neutrophils expressed CC chemokine receptor (CCR) 6, and the action of hBD-3 was completely abrogated by a neutralizing anti-CCR6 mAb. Collectively, these observations suggest that hBDs, especially hBD-3, can not only kill bacteria but also modulate (suppress) neutrophil apoptosis via the action on CCR6. Suppression of neutrophil apoptosis results in the prolongation of their lifespan and may be advantageous for the host defense against bacterial invasion.
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PMID:Evaluation of the effect of human beta-defensins on neutrophil apoptosis. 1830 14

Searching the database for mouse homologs of the antimicrobial peptide human beta-defensin-3 (hBD-3) revealed highest identity (69%) to mouse beta-defensin-14 (mBD-14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal activity. Treatment of keratinocytes with gamma interferon or transforming growth factor alpha increased mBD-14 gene expression. These data suggest that mBD-14 is the functional ortholog of hBD-3.
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PMID:Mouse beta-defensin-14, an antimicrobial ortholog of human beta-defensin-3. 1833 71

The human beta defensins (hBDs) 2 and 3 contribute to the inducible antimicrobial peptides in human skin. Besides an important role in fighting bacteria, they may also exert antiviral function. Verrucae vulgares and condylomata acuminata are typical cutaneous viral diseases caused by different subtypes of the human papillomavirus. Their tendency for spontaneous regression could be caused by antiviral proteins like defensins. In a retoperspective study, we investigated lesions of verrucae vulgares and condylomata acuminata for the presence of hBD-2 and hBD-3 by immunohistochemistry. All of the specimens of verrucae vulgares (n = 20) were positive for hBD-2 and hBD-3. The specimens of condylomata acuminata (n = 15) exhibited expression for hBD-2 and hBD-3, with the exception of three and two samples, respectively. The expression levels in condyloma acuminata were lower for both defensins compared with verrucae vulgares. Normal skin tissue exhibited no staining of both hBD-2 and hBD-3 with the exception of two cases. Taken together, this is the first report of an increased expression of the hBD-2 and hBD-3 in cutaneous papillomavirus infections.
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PMID:Expression of human beta-defensin-2 and -3 in verrucae vulgares and condylomata acuminata. 1835 3

Mycobacterium tuberculosis is a facultative intracellular pathogen capable of producing both progressive disease and latent infection. Latent infection is clinically asymptomatic and is manifested only by a positive tuberculin test or a chest radiograph that shows scars or calcified nodules indicative of resolved primary tuberculosis infection. In this study, we used a well-characterized model of latent tuberculosis infection in B6D2F1 mice to compare the production of beta-defensin-3 by infected bronchial epithelial cells and macrophages. We demonstrated by immunolectronmicroscopy that M. tuberculosis can actually infect epithelial cells and induce significant higher production of beta-defensin-3 associated to mycobacteria than infected macrophages. These results demonstrate that lung epithelium harbour mycobacteria during experimental chronic infection; being a possible reservoir of latent mycobacteria in vivo, beta-defensins might participate in bacilli killing or dormancy induction.
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PMID:The potential role of lung epithelial cells and beta-defensins in experimental latent tuberculosis. 1836 94

Leukotriene B(4) (LTB(4)) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB(4) lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB(4) receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as beta-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB(4). Viral loads in neutrophil-depleted mice were not diminished by LTB(4) administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB(4) led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB(4) receptor antagonists clearly demonstrate the implication of the high-affinity LTB(4) receptor in the LTB(4)-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB(4) against a viral pathogen.
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PMID:Leukotriene B4 induces release of antimicrobial peptides in lungs of virally infected mice. 1842 43

Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human beta-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine.
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PMID:Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. 1842 84

The ability of human beta-defensins hBD-1, hBD-2, and hBD-3 to exert direct in vitro antimicrobial effects was evaluated using Francisella tularensis Live Vaccine Strain (LVS) and Francisella novicida. While hBD-2 showed some antimicrobial activity in these assays, only hBD-3 demonstrated significant potency against Francisella. Francisella tularensis LVS infection induced elevated levels of hBD-2 mRNA in human airway epithelial (A549) cells, while having no significant impact on the levels of hBD-3 and only a moderate effect on the level of hBD-1 mRNA. Francisella infection avoided stimulating the production of the most potent anti-Francisella host peptide, hBD-3, in A549 cells, although hBD-3 is stimulated by other treatments. The differential induction of beta-defensins in Francisella infected lung epithelial cells suggests a complex dynamic in the expression of antimicrobial peptides and the innate immune response.
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PMID:Antimicrobial activity of human beta-defensins and induction by Francisella. 1845 6

Calcineurin inhibitors are potent inhibitors of T-cell-receptor mediated activation of the adaptive immune system. The effects of this class of drug on the innate immune response system are not known. Keratinocytes are essential to innate immunity in skin and rely on toll-like receptors (TLRs) and antimicrobial peptides to appropriately recognize and respond to injury or microbes. In this study we examined the response of cultured human keratinocytes to pimecrolimus. We observed that pimecrolimus enhances distinct expression of cathelicidin, CD14, and human beta-defensin-2 and beta-defensin-3 in response to TLR2/6 ligands. Some of these responses were further enhanced by 1,25 vitamin D3. Pimecrolimus also increased the functional capacity of keratinocytes to inhibit growth of Staphylococcus aureus and decreased TLR2/6-induced expression of IL-10 and IL-1beta. Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappaB in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense.
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PMID:Pimecrolimus enhances TLR2/6-induced expression of antimicrobial peptides in keratinocytes. 1849 69


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