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 2 (hBD-2) and hBD-3 have potent fungicidal activity in the micromolar range. Although little is known about their mechanism of action against Candida species, some similarities to the antifungal mechanism of salivary peptide histatin 5 (Hst 5) seem to exist. Since hBD-2 and hBD-3 have been reported to cause direct disruption of target cell membranes, we compared the effects of hBD-2 and hBD-3 on Candida albicans membrane integrity. Incubation of calcein-loaded C. albicans cells with a dose of hBD-2 lethal for 90% of the strains tested (LD(90)) resulted in a maximal dye efflux of only 10.3% +/- 2.8% at 90 min, similar to that induced by Hst 5. In contrast, an LD(90) of hBD-3 more than doubled calcein release from cells yet did not result in more than 24% of total release, showing that neither peptide caused gross membrane damage. As for Hst 5, killing of C. albicans cells by hBD-2 and hBD-3 was salt sensitive; however, Ca(2+) and Mg(2+) inhibited hBD-2 but not hBD-3 fungicidal activity. Pretreatment of C. albicans cells with sodium azide resulted in significantly decreased ATP release and susceptibility of cells to hBD-2 and hBD-3. However, hBD-3 killing was partially restored at concentrations of > or =0.8 microM, showing energy-independent mechanisms at higher doses. C. glabrata resistance to Hst 5, hBD-2, and hBD-3 is not a result of loss of expression of cell wall Ssa proteins. The candidacidal effects of hBD-2-hBD-3 and Hst 5-hBD-2 were additive, while the index of interaction between Hst 5 and hBD-3 was 0.717 (P < 0.05). Thus, the candidacidal action of hBD-2 shows many similarities to that of Hst 5 in terms of salt sensitivity, ion selectivity, and energy requirements while hBD-3 exhibits biphasic concentration-dependent mechanisms of candidacidal action complementary to those of Hst 5.
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PMID:Human beta-defensins kill Candida albicans in an energy-dependent and salt-sensitive manner without causing membrane disruption. 1707 97

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.
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PMID:Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections. 1718 89

Antimicrobial peptides human beta-defensins (hBD) are mainly produced by epithelia of several organs including skin, and participate in innate immunity by killing invading pathogens. Besides their microbicidal activities, hBD activate several inflammatory and immune cells. Since hBD are generated by tissues where mast cells are present, we hypothesized that these peptides could activate mast cells. In this study, we demonstrated that both hBD-3 and hBD-4 induced mast cell degranulation, prostaglandin D2 production, intracellular Ca2+ mobilization and chemotaxis. Furthermore, hBD-3- and hBD-4-induced activation of mast cells was suppressed by pertussis toxin and U-73122, inhibitors for G protein and phospholipase C, respectively. We further revealed that hBD-3 and hBD-4 increased vascular permeability in the skin, which was dependent on the presence of mast cells, because hBD-3 and hBD-4 failed to enhance vascular permeability in mast cell-deficient Ws/Ws rats. We also demonstrated that hBD-3 and hBD-4 induced phosphorylation of MAPK p38 and ERK1/2, which were further required for hBD-mediated mast cell activation, as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on mast cell degranulation. Together, these findings suggest the key role of hBD in inflammatory responses by recruiting and activating mast cells, and increasing vascular permeability.
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PMID:Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. 1723 Apr 40

"Streptococcal inhibitor of complement" (SIC) and "distantly related to SIC" (DRS) are related virulence factors secreted by M1 and M12 strains of GAS, respectively. The human mucosal innate immune system, important components of which are beta-defensins, secretory leukocyte proteinase inhibitor (SLPI) and lysozyme, provides the first line of defence against microorganisms. We report the interaction between DRS and these proteins; further investigations into the interaction of SIC with the beta-defensins; and compare the sensitivity of M12 and M1 GAS to SLPI. We show that SLPI, which kills M1 GAS and is inhibited by SIC, cannot kill M12 GAS. DRS cannot inhibit SLPI killing of M1 GAS, although ELISA shows binding of DRS to SLPI. We suggest that the target for SLPI on M1 GAS resembles SIC, and soluble SIC inhibits by acting as a decoy for SLPI. M12 GAS may not have this target and cannot interact with SLPI. DRS inhibits the antibacterial action of hBD-2 and hBD-3. Binding of both SIC and DRS to hBD-2, and DRS to hBD-3, shows small positive enthalpy, suggesting that binding is largely hydrophobic. The data for SIC and hBD-3 indicate that this is not a homogeneous bimolecular interaction. We conclude that DRS shares several of the properties of SIC, and therefore can be considered an important virulence factor of M12 GAS and an aid to colonization of the host mucosae.
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PMID:Streptococcal DRS (distantly related to SIC) and SIC inhibit antimicrobial peptides, components of mucosal innate immunity: a comparison of their activities. 1730 63

The aim of this study was to determine the content and/or composition of protein, peptide, amino acid, lipid and fatty acid in bacterial douchi (BD) made by different pure starter fermentation. Protein content of BD3, BD5, BD7 and BD8 was significantly higher than that of autoclaved soybean (AS). Lipid content of BD1, BD5 and BD6 was also significantly higher than that of AS. Predominant amino acids were glutamic acid (11.3-15.2%), proline (11.2-14.5%), aspartic acid (8.7-10.0%), leucine (9.2-10.0%) and alanine (7.4-8.9%). BD had EAA7 and EAA9 values of 34.4-36.4% and 40.5-41.7% respectively. Threonine with the amino acid score of 61-85 was the limiting amino acid. Triacylglycerol (82.4-88.2%) was the most abundant lipid in BD, followed by phospholipid (9.6-16.4%) and phytosterol (1.2-2.9%). Major fatty acids were palmitic (10.6-11.3%), oleic (20.5-21.9%), linoleic (54.2-55.6%) and alpha-linolenic acid (8.2-9.1%). The ratio of n-6 polyunsaturated fatty acids (PUFA) to n-3 PUFA ranged from 6.1 to 6.7. Amino acid nitrogen and trichloroacetic acid soluble protein increased from 0.2% (AS) to 1.8% (BD8) and from 1.3% (AS) to 4.0% (BD7) at the highest level respectively. Peptides with molecular weight < or = 2000Da accounted for at least 75% of total peptide. Bacterial fermentation of soybean increased amino acid nitrogen and trichloroacetic acid soluble protein except BBDC6, decreased molecular weight of 100-500 and increased 500-1000 and 2000-5000 peptides. Composition of lipids, fatty acids, and amino acids were no significant change after soybean bacterial fermentation.
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PMID:Nutritional evaluation of different bacterial douchi. 1739 7

The human beta-defensins (hBDs) are peptides with a strong antimicrobial activity. Patients with atopic dermatitis (AD) and mycosis fungoides (MF) are prone to skin infections. We aimed to investigate the mRNA expression of hBDs in lesional and non-lesional skin of MF patients, and to compare the data with hBD levels found in AD patients and healthy controls. In this prospective pilot study, 13 patients with MF were recruited. Punch biopsies were harvested from the centre of the tumour (lesional) as well as a healthy skin site (non-lesional controls). In addition to the specimens of MF patients, skin samples (healthy controls) were obtained from healthy subjects (n = 15) and patients with acute AD (n = 14). In order to detect mRNA of hBDs, we performed quantitative real-time reverse transcriptase polymerase chain reaction. As compared to healthy controls, skin of patients with MF (non-lesional and lesional) and AD patients showed significantly lower hBD-1 mRNA expression and significantly higher hBD-2 and hBD-3 mRNA expression. HBD-1 mRNA levels of lesional skin were significantly lower than those of non-lesional skin. By contrast, significantly increased hBD-2 and hBD-3 mRNA expression was found in lesional skin of MF patients when compared to non-lesional skin. HBD mRNA expression in lesional skin of MF patients did not significantly differ from hBD expression that was observed in AD lesions. We observed an identical pattern of hBD expression in MD and AD suggesting a common regulatory mechanism that might mainly be driven by T helper 2 lymphocytes.
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PMID:Expression of human beta-defensins in patients with mycosis fungoides. 1741 76

Nasal carriage of Staphylococcus aureus is an important source of nosocomial infection and community-acquired methicillin-resistant S. aureus (MRSA). Previous studies by our laboratory revealed that nasal carriage of S. aureus is accompanied by subclinical inflammation, which is insufficient to prevent colonization, and that carriage might also be a result of adaptation and selection of certain S. aureus strains to the host's nasal environment. In the present study we observed that a carrier strain of S. aureus preferentially colonizes and attaches to nasal epithelial cells (NEC) compared to a non-carrier S. aureus strain. Conversely, when naive NEC were pretreated with interleukin-1beta for 24 hr, the growth and attachment of the carrier strain of S. aureus were significantly reduced in comparison to the non-carrier strain, emphasizing the pivotal role played by host innate immunity in the initial events of nasal carriage. While both strains up-regulated the expression of the pattern recognition receptor, Toll-like receptor 2 (TLR2), NEC exposed to the nasal carrier strain had a 4-hr delay in TLR2 expression compared with NEC exposed to non-carrier S. aureus. Moreover, even after 20 hr of colonization the expression of two principal epithelial antimicrobial peptides, human beta-defensin-2 and human beta-defensin-3, was negligibly induced in NEC exposed to the nasal carrier strain of S. aureus in comparison to the non-carrier strain. These results suggest that carrier strains of S. aureus retain a competitive advantage over non-carrier strains by delaying the host's innate response to epithelial colonization and infection.
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PMID:Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium. 1747 20

There is increasing evidence that innate and adaptive immune responses are intimately linked. This linkage is in part mediated through the recognition of conserved microbial products by Toll-like receptors (TLRs). Detection of microbial products by TLRs can result in induction of inflammatory cytokines and activation of professional antigen-presenting cells, thereby enhancing adaptive immune responses. Here, we show that human beta-defensin-3 (hBD-3), an innate antimicrobial peptide, can induce expression of the costimulatory molecules CD80, CD86, and CD40, on monocytes and myeloid dendritic cells in a TLR-dependent manner. Activation of monocytes by hBD-3 is mediated by interaction with TLRs 1 and 2, resulting in signaling that requires myeloid differentiating factor 88 and results in IL-1 receptor-associated kinase-1 phosphorylation. In studies with HEK cells engineered to express various TLRs, we show that activation of NF-kappaB by hBD-3 depends on the expression of both TLR1 and TLR2. Thus, human TLR signaling is not restricted to recognition of microbial patterns but also can be initiated by host-derived peptides such as hBD-3.
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PMID:Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. 1800 61

Human beta-defensin-3(HBD3) is a low molecular weight cationic peptide with a broad antimicrobial spectrum. A recombinant Escherichia coli (pET32-smHBD3) was constructed to produce HBD3 fusion protein (TrxA-HBD3) before, but the productivity is relatively low. In the present work, the effects of different expression conditions were systematically investigated to improve the expression level of the fusion protein. With regard to the volumetric productivity, the optimal conditions were determined as follows: cultivation at 34 degrees C in MBL medium, induction at middle stage of the exponential growth phase with 0.4 mM isopropylthio-D-galactoside, and postinduction expression for 8 h. Under these conditions, the volumetric productivity of the fusion protein reached 2.55 g/L, i.e., 0.55 g mature HBD3/L, which was about 2.6 times of that obtained under the unoptimized conditions. And the target protein still maintained high solubility (> or =97.9%) and accounted for 66% of the total soluble protein. A cationic exchange purification step was employed to obtain high-purity target protein (90%) with a recovery ratio of 78%. This soluble expression level of HBD3 fusion protein was the highest among all the reported literature and facilitated the development of high efficient purification of HBD3.
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PMID:Enhanced expression and primary purification of soluble HBD3 fusion protein in Escherichia coli. 1802 75

Recent findings indicate a principal role for Hepcidin in iron homeostasis. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. Under normal conditions influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin. Ferroportin is a Hepcidin binding protein expressed in duodenal enterocytes. Hepcidin is a peptide synthesised in the liver and is the main regulator of iron homeostasis. It is a defensin like protein and exhibits anti-microbial and anti-fungal activity. The Hepcidin gene is principally expressed in hepatocytes but to a lesser extent in neutrophils and macrophages. Hereditary Haemochromatosis is caused by disruption of iron homeostasis due to mutations in the HFE gene (C282Y or H63D). Unrestricted uptake of iron by duodenal enterocytes causes iron overload which is the hallmark of the disease. Current thinking is that defective Hepcidin synthesis or defective iron-sensing mechanisms leading to Hepcidin deficiency is the cause of iron overload in HFE-Haemochromatosis. Thus HFE-Haemochromatosis has been described as an endocrine disease. Basal levels of Hepcidin appear to be normal in HFE-Haemochromatosis patients. This contradicts current theories of defective Hepcidin synthesis as the cause of Hereditary HFE-Haemochromatosis. We propose that the defect in HFE-Haemochromatosis is the loss of Hepcidin surge in response to intake of dietary iron and is not as a result of reduced synthesis.
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PMID:Defective release of Hepcidin not defective synthesis is the primary pathogenic mechanism in HFE-Haemochromatosis. 1805 40


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