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)

Defensins represent a major component of innate host defense against bacteria, fungi, and enveloped viruses. One potent defensin found, e.g., in epithelia, is the polycationic human beta-defensin-3 (hBD3). We investigated the role of the lipid matrix composition, and in particular the presence of negatively charged lipopolysaccharides (LPS) from sensitive (Escherichia coli, Salmonella enterica serovar Minnesota) or resistant (Proteus mirabilis) Gram-negative bacteria or of the zwitterionic phospholipids of human cells, in determining the action of polycationic hBD3 on the different membranes, and related to their biological activity. The main focus was directed on data derived from electrical measurements on a reconstitution system of the OM as a planar asymmetric bilayer composed on one side of LPS and on the other of a phospholipid mixture. Our results demonstrate that the antimicrobial activity and the absence of cytotoxicity can be explained by the lipid-specificity of the peptide. A clear correlation between these aspects of the biological activity of hBD3 and its interaction with lipid matrices could be found. In particular, hBD3 could only induce lesions in those membranes resembling the lipid composition of the OM of sensitive bacterial strains. The permeation through the membrane is a decisive first step for the biological activity of many antimicrobial peptides. Therefore, we propose that the lipid-specificity of hBD3 as well as some other membrane-active antimicrobial peptides is important for their activity against bacteria or mammalian cells.
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PMID:Lipid-specific membrane activity of human beta-defensin-3. 1663 47

A codon optimized mature human beta-defensin-3 gene (smHBD3) was synthesized and fused with TrxA to construct pET32-smHBD3 vector, which was transformed into E. coli BL21(DE3) and cultured in MBL medium. The volumetric productivity of fusion protein reached 0.99 g fusion protein l(-1), i.e. 0.21 g mature HBD3 l(-1). Ninety-six percentage of the fusion protein was in a soluble form and constituted about 45% of the total soluble protein. After cell disruption, the soluble fusion protein was separated by affinity chromatography and cleaved by enterokinase, and then the mature HBD3 was purified by cationic ion exchange chromatography. The overall recovery ratio of HBD3 was 43%. The purified mature HBD3 demonstrated antimicrobial activity against E. coli.
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PMID:Production of bioactive human beta-defensin-3 in Escherichia coli by soluble fusion expression. 1664 99

Defensins in innate immunity are known to play critical roles to protect the host from infection by invasive microbes, including Gram-positive and -negative bacteria. However, little is known about the interactions between defensins and mycoplasmas. Human beta defensin (hBD)-2 and hBD-3, but not hBD-1, were found to exert strikingly antimicrobial activity against Mycoplasma pneumoniae. To elucidate the role of defensins in M. pneumoniae infection, a human pulmonary squamous cell line EBC-1 was stimulated with M. pneumoniae and interleukin (IL)-1beta. hBD-2 was markedly upregulated by IL-1beta as well as M. pneumoniae, but neither hBD-1 nor hBD-3 was apparently upregulated. Thus, the results suggest that inducible hBD-2 would play a critical role in the protection of M. pneumoniae infection.
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PMID:Antimicrobial activity of inducible human beta defensin-2 against Mycoplasma pneumoniae. 1673 51

We found that sterile wounding of human skin induced epidermal expression of the antimicrobial (poly)peptides human beta-defensin-3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor through activation of the epidermal growth factor receptor. After skin wounding, the receptor was activated by heparin-binding epidermal growth factor that was released by a metalloprotease-dependent mechanism. Activation of the epidermal growth factor receptor generated antimicrobial concentrations of human beta-defensin-3 and increased the activity of organotypic epidermal cultures against Staphylococcus aureus. These data demonstrate that sterile wounding initiates an innate immune response that increases resistance to overt infection and microbial colonization.
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PMID:Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor. 1677 86

Previously, we showed that human epithelial cell-derived beta-defensins (hBD)-2 and -3 block HIV-1 replication via a direct interaction with virions and through modulation of the CXCR4 coreceptor on immunocompetent cells. In the present study, we show that hBD-3 promotes directly the internalization of CXCR4 yet does not induce calcium flux, ERK (ERK-1/2) phosphorylation, or chemotaxis. hBD-3 competes with stromal-derived factor 1 (SDF-1), the natural ligand for CXCR4, for cellular binding and blocks SDF-1-induced calcium flux, ERK-1/2 phosphorylation, and chemotaxis, without effects on other G protein-coupled receptors. The novel activity of this endogenous CXCR4 antagonist may provide a new strategy for HIV therapies or immunomodulation. Moreover, since the SDF-1/CXCR4 axis plays an important role in hemopoiesis, neurogenesis, cardiogenesis, and angiogenesis, endogenous agents such as hBD-3 or its derivatives offer a new paradigm in immunoregulatory therapeutics and provide the opportunity to enhance future drug design.
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PMID:Cutting edge: human beta defensin 3--a novel antagonist of the HIV-1 coreceptor CXCR4. 1681 31

Despite enormous progress, the DNA sequencing of difficult regions, whether they are part of complex genomes or individual constructs, still presents a significant challenge and may require many trials, brute-force, or the intervention of a very experienced sequencer (and sometimes all of the above). Very early on, it was realized that sequencing of various types of difficult templates requires distinct treatments. To sequence through GC-rich regions, the addition of DMSO, NP-40/Tween-20 detergents, or the mix (4:1) of BD3.0:dGTP3.0 was sometimes helpful. To get through long poly-A/T tails, sometimes one would be successful using tailored poly- A/T (V/B) N primers or primers that spanned part of pre-tail and tail regions. A few years ago invitrogen introduced a set of sequencing additives that proved to be useful for many different types of difficult templates.
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PMID:Fundamentals of sequencing of difficult templates--an overview. 1687 Jul 12

The presence of antimicrobial peptides (AMPs) in saliva may be a biological factor that contributes to susceptibility or resistance to caries. This manuscript will review AMPs in saliva, consider their antimicrobial and immunomodulatory functions, and evaluate their potential role in the oral cavity for protection of the tooth surface as well as the oral mucosa. These AMPs are made in salivary gland and duct cells and have broad antimicrobial activity. Alpha-defensins and LL37 are also released by neutrophils into the gingival crevicular fluid. Both sources may account for their presence in saliva. A recent study in middle school children aimed to determine a possible correlation between caries prevalence in children and salivary concentrations of the antimicrobial peptides human beta-defensin-3 (hBD-3), the cathelicidin, LL37, and the alpha-defensins. The levels of these AMPs were highly variable in the population. While levels of LL37 and hBD-3 did not correlate with caries experience, the mean alpha-defensin level was significantly higher in children with no caries than in children with caries (p < 0.005). We conclude that several types of AMPs that may have a role in oral health are present in unstimulated saliva. Low salivary levels of alpha-defensin may represent a biological factor that contributes to caries susceptibility. Our observation could lead to new ways to prevent caries and to a new tool for caries risk assessment.
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PMID:Oral antimicrobial peptides and biological control of caries. 1693 14

A group of interesting molecules called defensins exhibit multiple functions but have been primarily recognized to possess a broad spectrum of antimicrobial activities. Studies have reported two different types of defensins (alpha and beta) from human and animals, a cyclic theta defensin from rhesus, and several defensin-like peptides from plants. There is no amino acid sequence homology between these peptides, but they all contain three Cys-Cys disulfide linkages while the connectivities are different. Human beta-defensin-3 (HbetaD-3) is the most recently discovered member of the host-defense peptide family that has attracted much attention. This molecule is expressed either constitutively or induced upon a challenge, and a growing evidence indicates the involvement of such molecules in adaptive immunity as well. It has been shown to exhibit antibacterial activities towards Gram-negative and Gram-positive bacteria as well as an ability to act as a chemo-attractant. Analysis of NMR structural data suggested a symmetrical dimeric form of this peptide in solution, which consists of three beta strands and a short helix in the N-terminal region. While the disulfide linkages are known to provide the structural stability and stability against proteases, the biological relevance of this dimeric form was contradicted by another biological study. Since there is considerable current interest in developing HbetaD-3 for possible pharmaceutical applications, studies to further our understanding on the determinants of antibacterial activities and immunomodulatory function of HbetaD-3 are considered to be highly significant. The knowledge of its biosynthetic regulation will also help in understanding the role of HbetaD-3 in immunity. This article presents an overview of the expression and regulation of HbetaD-3 in humans, and the structure-function correlations among HbetaD-3 and its modified peptides are discussed emphasizing the functional importance. The future scope for studies on HbetaD-3 and design of short potent antimicrobial peptides, based on the native HbetaD-3 molecule, that do not interfere in the immunomodulatory function is also outlined.
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PMID:The human beta-defensin-3, an antibacterial peptide with multiple biological functions. 1697 80

Anti-microbial peptides produced from mucosal epithelium appear to play pivotal roles in the host innate immune defence system in the oral cavity. In particular, human beta-defensins (hBDs) and the cathelicidin-type anti-microbial peptide, LL-37, were reported to kill periodontal disease-associated bacteria. In contrast to well-studied hBDs, little is known about the expression profiles of LL-37 in gingival tissue. In this study, the anti-microbial peptides expressed in gingival tissue were analysed using immunohistochemistry and enxyme-linked immunosorbent assay (ELISA). Immunohistochemistry revealed that neutrophils expressed only LL-37, but not hBD-2 or hBD-3, and that such expression was prominent in the inflammatory lesions when compared to healthy gingivae which showed very few or no LL-37 expressing neutrophils. Gingival epithelial cells (GEC), however, expressed all three examined anti-microbial peptides, irrespective of the presence or absence of inflammation. Moreover, as determined by ELISA, the concentration of LL-37 in the gingival tissue homogenates determined was correlated positively with the depth of the gingival crevice. Stimulation with periodontal bacteria in vitro induced both hBD-2 and LL-37 expressions by GEC, whereas peripheral blood neutrophils produced only LL-37 production, but not hBD-2, in response to the bacterial stimulation. These findings suggest that LL-37 displays distinct expression patterns from those of hBDs in gingival tissue.
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PMID:Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue. 1703 73

The field of naturally occurring antimicrobial peptides is a research area rapidly expanding due to the high potential of such molecules as new antimicrobial drugs. In this regard, the human beta-defensin-3 is particularly attractive because of its strong antibacterial activity, relative salt-insensitiveness and low toxicity for host cells.
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PMID:Human beta-defensin-3: a promising antimicrobial peptide. 1707 6


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