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)

Human beta-defensin-3 (HBD3), an endogenous antimicrobial peptide, has strong broad-spectrum antimicrobial activity. This study aimed to obtain recombinant HBD3 (rHBD3) and to test the hypothesis that the antimicrobial characteristics of HBD3 may offer an advantage over conventional medicine in reducing intracanal bacteria. Genetic engineering was used to obtain active rHBD3 and analysis revealed that it exhibited a broad spectrum of antibacterial activity at low micromolar concentrations against not only Staphylococcus aureus and Escherichia coli but also against some critical pathogenic microbes in infected root canals, including Fusobacterium nucleatum, Prevotella melaninogenica, Peptostreptococcus anaerobius, Streptococcus mutans, Actinomyces naeslundii, Enterococcus faecalis and Candida albicans. In an in vitro antibacterial experiment, rHBD3 significantly eliminated pathogenic bacteria in root canals. The ratio of bacterial death was up to 98%. We conclude that HBD3 has the potential to eliminate bacteria effectively and rapidly in the local microenvironment of the root canal system and that it may contribute to successful endodontic treatment.
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PMID:In vitro bactericidal activity of recombinant human beta-defensin-3 against pathogenic bacterial strains in human tooth root canal. 1877 47

Although antimicrobial peptides (AMPs) appear to have diverse functional activities in innate immunity, a few reports suggest a potential role of human beta-defensin (hBD)-1 in tumor suppression. The aim of the present study was to compare the expression patterns of hBD-1, -2 and -3 in various features of human salivary gland tissues, such as healthy parenchyma, chronic sialadenitis and intraglandular pleomorphic adenomas, with their adjacent normal tissues. Twenty human salivary gland specimens (five healthy, five chronic sialadenitis, five pleomorphic adenomas and five adenoma adjacent normal tissues (AANTs)) were investigated for mRNA expression levels of hBD-1, -2 and -3 by quantitative real-time RT-PCR. Additionally, immunohistochemistry for the hBD-1, -2 and -3 peptides was performed for analysis of localization. Considerably increased, 80-fold higher hBD-1 and increased hBD-3 mRNA expression levels compared to healthy salivary gland tissues were detected in chronic sialadenitis. In pleomorphic adenomas hBD-2 expression levels were lower, but hBD-1 expression levels were significant decreased (p=0.03) compared to healthy parenchyma. Interestingly, the AANTs showed a 48-fold higher expression of hBD-1 and increased hBD-3 expression compared to the healthy salivary gland. Immunohistochemistry of the tumors showed nuclear hBD-1 localization. For the first time, it was shown that hBD-1 gene expression is significantly decreased in pleomorphic adenomas, while simultaneously the protein is localized in the nucleus. Increased expression levels in glandular inflammation have been described previously albeit not in AANTs. These data support the hypothesis that hBD-1 might be a potential tumor suppressor also in benign salivary gland tumors in addition to other genetic alterations.
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PMID:Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic adenomas of salivary glands. 1880 29

Maxillofacial silicone elastomer, when used as a prosthesis, is in contact with wound surfaces and mucosa, and tends to be contaminated with microorganisms from a patient's saliva and blood. The aim of the study was to evaluate the efficacy of human beta-defensin-3 (HBD3) on the reduction of two resistant bacteria species from the surface of maxillofacial silicone elastomer. HBD3 cDNA was amplified from total RNA, which had been extracted from human gingival epithelium by means of reverse-transcription polymerase chain reaction (RT-PCR). Following this, the cDNA fragments were recombined in a prokaryotic expression vector. The constructed expression vectors pET-32a/HBD3 were transformed into Escherichia coli to obtain recombinant protein. After protein purification and refolding, the product was verified in classic antimicrobial experiments against Staphylococcus aureus and Candida albicans. Specimens made of silicone elastomer A-2186, which had been contaminated with S. aureus or C. albicans, were immersed in rHBD3 or 5.25% sodium hypochlorite (a positive control) for 5 min, 10 min, 30 min, or 60 min. The active recombinant HBD3 obtained in the current study eliminated the S. aureus and C. albicans microorganism from the surface of the maxillofacial elastomer after a 30-min immersion. There was no statistically significant difference between the rHBD3 group and the sodium hypochlorite 5.25% group. In conclusion, rHBD3 exhibits antibacterial activity against oral pathogenic strains that adhere to maxillofacial elastomer, and may, thus, contribute to the prevention of infections caused by S. aureus and C. albicans.
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PMID:Disinfection of maxillofacial silicone elastomer using a novel antimicrobial agent: recombinant human beta-defensin-3. 1884 2

Gram-positive bacterial bone infections are an important cause of morbidity particularly in immunocompromised patients. Antimicrobial peptides (AP) are effectors of the innate immune system and directly kill microorganisms in the first hours after microbial infection. The aim of the present investigation was to study the expression and regulation of gram-positive specialized human beta-defensin-3 (HBD-3) in bone. Samples of healthy and osteomyelitic human bone were assessed for the expression of HBD-3. Using primary and immortalized osteoblasts (SAOS-2 cells), release and regulation of HBD-3 was evaluated after exposure to Staphylococcus aureus supernatant and/or corticosteroids using PCR, immunohistochemistry, Western blot and ELISA. To determine the role of toll-like-receptors-2 and -4 (TLR-2/-4), shRNA was used to downregulate TLRs. An osteomyelitis mouse model was created performed to investigate the release of murine beta-defensins using immunohistochemistry and RT-PCR. Cultured osteoblasts and human bone produce HBD-3 under standard conditions. The release increases within hours of bacterial supernatant exposure in cultured osteoblasts. This observation was not made in chronically infected bone samples. The shRNA-technology revealed the necessity of TLR-2 and -4 in HBD-3 induction in osteoblasts. Blocking protein synthesis with cycloheximide showed that the rapid release of HBD-3 is not dependent on a translational de novo synthesis and is not affected by glucocorticoids. The murine osteomyelitis model confirmed the in vivo release uptake of mouse beta-defensins-4 (MBD-4) in bone. This report shows the bacterial induction of HBD-3 via TLR-2 and -4 in osteoblasts and suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection. The rapid and effective induction of HBD-3 in osteoblasts incubated with conditioned media from bacteria is more likely a result of a rapid secretion of preformed HBD-3 by osteoblasts rather than a result of enhanced biosynthesis. The increased incidence of gram-positive bacterial bone infection in patients with regular intake of glucocorticoids does not seem to be caused by a deranged HBD-3 release in osteoblasts.
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PMID:Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3. 1892 11

ABSTRACT Epidemics of aster yellows in lettuce in Ohio are caused by at least seven distinct phytoplasma strains in the aster yellows (AY) group. Five of the strains are newly reported: AY-BW, AY-WB, AY-BD3, AY-SS, and AY-SG. All seven strains were characterized based on symptoms in aster and lettuce, and by polymerase chain reaction (PCR). Strain AY-BD2 (formerly 'Bolt') causes yellowing and leaf distortion in lettuce and bolting in aster, whereas strain AY-S (formerly 'Severe') causes stunting, leaf clustering, and phyllody. Strain AY-WB causes yellowing and wilting in lettuce and witches'-broom in aster. Strain AY-SG induces horizontal growth in lettuce and aster plants. Strain AY-BW causes chlorosis of emerging leaves and abnormally upright growth of leaf petioles. AY-SS causes symptoms similar to those caused by AY-S but has a different PCR-restriction fragment length polymorphism (RFLP) banding pattern. Strains AY-BD2 and AY-BD-3 cause mild leaf and stem distortion in lettuce but are differentiated by PCR-RFLP. All phytoplasma strains collected from lettuce in Ohio belong to the 16SrI group. AY-WB belongs to the 16SrI-A subgroup and the other six belong to the 16SrI-B subgroup. Five of the seven strains were distinguished from each other by primer typing. The results of phylogenetic analyses of sequences of the 16S rRNA genes were basically consistent with the classification based on PCR-RFLP, in which AY-WB clustered with phytoplasmas of the 16rIA subgroup and the other Ohio lettuce strains clustered with phytoplasmas in the 16SrI-B subgroup.
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PMID:Molecular and symptom analyses of phytoplasma strains from lettuce reveal a diverse population. 1894 4

Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacterial bone infection. An osteomyelitis mouse model confirmed the osseous induction of the murine homologue of human beta-defensin-2, suggesting a central role in the prevention of bacterial bone infection. Antimicrobial peptides are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Some of them are produced constitutively, whereas others are induced during infection. Human beta-defensins represent a major subclass of antimicrobial peptides and act as a first line of defence through their broad spectrum of potent antimicrobial activity. The aim of the present in-vitro and in-vivo investigations was to study the expression and regulation of human beta-defensin-2 in the case of bacterial bone infection and to analyse the effects of immunosuppressive drugs on bone-derived antimicrobial peptide expression. Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the expression of human beta-defensin-2. Regulation of human beta-defensin-2 was studied in hFOB cells after exposure to bacterial supernatants, proinflammatory cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was assayed by enzyme-linked immunosorbent assay. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologue of human beta-defensin-2, named murine beta-defensin-3, by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Healthy human bone and cultured osteoblasts are able to produce human beta-defensin-2 under standard conditions. Samples of infected bone produce higher levels of endogenous antibiotics, such as human beta-defensin-2, when compared with samples of healthy bone. A clear induction of human beta-defensin-2 was observed after exposure of cultured osteoblasts to gram-positive bacteria or proinflammatory cytokines. Additional treatment with glucocorticoids or methotrexate prevented bacteria-mediated antimicrobial peptide induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional upregulation of the murine homologue of human beta-defensin-2, namely murine beta-defensin-3, in bone after intraosseous contamination of the tibia. Human and murine bone have the ability to produce broad-spectrum endogenous antibiotics when challenged by micro-organisms in vitro and in vivo. Immunosuppressive drugs, such as glucocorticoids or methotrexate, may increase the susceptibility to bone infection by decreasing antimicrobial peptide expression levels in case of microbial challenge. The induction of human beta-defensin-2 following bacterial contact suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection.
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PMID:The role of human beta-defensin-2 in bone. 1909 91

Human beta-defensins (hBDs) are small, cationic antimicrobial peptides produced by oral and other mucosal epithelia. More recently, hBDs have been shown to regulate adaptive immunity. In this study, we provide new information about the potential role of hBD-3 in the progression of oral cancer. In normal human oral epithelia, hBD-3 is produced by mitotically active cells in the basal layers of oral epithelium, whereas hBD-1 and -2 are coexpressed in the differentiated spinosum and granulosum layers. Interestingly, premalignant cells in carcinoma in situ lesions overexpress hBD-3, but not hBD-1 and hBD-2, correlating with specific recruitment and infiltration of macrophages. Our in vitro studies demonstrate that hBD-3 chemoattracts THP-1 monocytic cells and that epidermal growth factor (EGF) significantly induces hBD-3 expression in oral epithelial cells via mitogen-activated protein kinase (MAPK) kinase MEK1/2, p38 MAPK, protein kinase C (PKC), and phosphoinositide 3 kinase (PI3K), but not via Janus kinase (JAK) and signal transducer and activator of transcription (STATs). These results suggest that hBD-3 serves as a mitogen responsive gene in the initiation of oral cancer and may act as a motility signal to recruit tumor-associated macrophages.
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PMID:Overexpression of human beta-defensin-3 in oral dysplasia: potential role in macrophage trafficking. 1909 30

Antimicrobial peptides (AMPs) such as defensins and cathelicidins are small peptides with broad-spectrum activity against bacteria, fungi and viruses. In addition, several AMPs modulate mammalian cell behaviours including migration, proliferation and cytokine production. This review describes findings from recent studies showing the presence of various AMPs at the human ocular surface and discusses their mechanism of antimicrobial action and potential non-microbicidal roles. Corneal and conjunctival epithelial cells produce beta-defensins and the cathelicidin LL-37, whereas neutrophils, infiltrating in response to a specific stimulus, supply additional LL-37 as well as alpha-defensins. In vitro studies suggest that LL-37 and human beta-defensin-3 are the most likely to have significant independent antimicrobial activity, while other AMPs may act synergistically to help protect the ocular surface from invading pathogens. Current evidence also supports a role for some AMPs in modulating wound healing responses. Although yet to be brought to fruition, AMPs hold significant potential as therapeutic agents for the prophylaxis and treatment of infection, promotion of wound healing and immune modulation.
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PMID:The role of antimicrobial peptides at the ocular surface. 1912 67

Antimicrobial peptides (AMPs) are secreted in the airway and contribute to initial defence against inhaled pathogens. Infections of the respiratory tract are a major cause of morbidity and mortality in preterm newborns and in patients with cystic fibrosis (CF). In this latter group, the state of chronic lung infection is due to the ability of bacteria to grow as mucoid biofilm, a condition characterised by overproduction and release of polysaccharides (PSs). In this study, we investigate the effect of PSs produced by lung pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae and members of the Burkholderia cepacia complex on the antibacterial activity of structurally different peptides. The AMPs tested in this study include the cathelicidin LL-37 and the beta-defensin hBD-3 from humans, both released at the alveolar level, as well as peptides from other mammals, i.e. SMAP-29, PG-1 and Bac7(1-35). Susceptibility assays, time killing and membrane permeabilization kinetics experiments were carried out to establish whether PSs produced by lung pathogens may be involved in the poor defence reaction of infected lungs and thus explain infection persistence. All the PSs investigated inhibited, albeit to a different extent, the antibacterial activity of the peptides tested, suggesting that their presence in the lungs of patients with CF may contribute to the decreased defence response of this district upon infection by PS-producing microorganisms. The results also show that inhibition of the antibacterial activity is not simply due to ionic interaction between the negatively charged PSs and the cationic AMPs, but it also involves other structural features of both interactors.
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PMID:Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens. 1946 93

Defensins are small (3-5 kDa) cysteine-rich cationic proteins found in both vertebrates and invertebrates constituting the front line of host innate immunity. Despite intensive research, bactericidal and cytotoxic mechanisms of defensins are still largely unknown. Moreover, we recently demonstrated that small peptides derived from defensins are even more potent bactericidal agents with less toxicity toward host cells. In this paper, structures of three C-terminal (R36-K45) analogues of human beta-defensin-3 were studied by 1H NMR spectroscopy and extensive molecular dynamics simulations. Because of indications that these peptides might target the inner bacterial membrane, they were reconstituted in dodecylphosphocholine or dodecylphosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] mixed micelles, and lipid bicelles mimicking the phospholipid-constituted bilayer membrane of mammalian and bacterial cells. The results show that the binding affinity and partitioning into the lipid phase and the ability to dimerize and accrete well-defined structures upon interactions with lipid membranes contribute to compactization of positive charges within peptide oligomers. The peptide charge density, mediated by corresponding three-dimensional structures, was found to directly correlate with the antimicrobial activity. These novel observations may provide a new rationale for the design of improved antimicrobial agents.
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PMID:Structure-dependent charge density as a determinant of antimicrobial activity of peptide analogues of defensin. 1958 Mar 34


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