Defensins
Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands. (1/685)
beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at mucosal surfaces. Two human beta-defensins, HBD-1 and HBD-2, were discovered in 1995 and 1997, respectively. However, little is known about the expression of HBD-1 or HBD-2 in tissues of the oral cavity and whether these proteins are secreted. In this study, we characterized the expression of HBD-1 and HBD-2 mRNAs within the major salivary glands, tongue, gingiva, and buccal mucosa and detected beta-defensin peptides in salivary secretions. Defensin mRNA expression was quantitated by RNase protection assays. HBD-1 mRNA expression was detected in the gingiva, parotid gland, buccal mucosa, and tongue. Expression of HBD-2 mRNA was detected only in the gingival mucosa and was most abundant in tissues with associated inflammation. To test whether beta-defensin expression was inducible, gingival keratinocyte cell cultures were treated with interleukin-1beta (IL-1beta) or bacterial lipopolysaccharide (LPS) for 24 h. HBD-2 expression increased approximately 16-fold with IL-1beta treatment and approximately 5-fold in the presence of LPS. Western immunoblotting, liquid chromatography, and mass spectrometry were used to identify the HBD-1 and HBD-2 peptides in human saliva. Human beta-defensins are expressed in oral tissues, and the proteins are secreted in saliva; HBD-1 expression was constitutive, while HBD-2 expression was induced by IL-1beta and LPS. Human beta-defensins may play an important role in the innate defenses against oral microorganisms. (+info)Efficient killing of inhaled bacteria in DeltaF508 mice: role of airway surface liquid composition. (2/685)
Cystic fibrosis mice have been generated by gene targeting but show little lung disease without repeated exposure to bacteria. We asked if murine mucosal defenses and airway surface liquid (ASL) Cl(-) were altered by the DeltaF508 cystic fibrosis transmembrane conductance regulator mutation. Naive DeltaF508 -/- and +/- mice showed no pulmonary inflammation and after inhaled Pseudomonas aeruginosa had similar inflammatory responses and bacterial clearance rates. We therefore investigated components of the innate immune system. Bronchoalveolar lavage fluid from mice killed Escherichia coli, and the microbicidal activity was inhibited by NaCl. Because beta-defensins are salt-sensitive epithelial products, we looked for pulmonary beta-defensin expression. A mouse homolog of human beta-defensin-1 (termed "MBD-1") was identified; the mRNA was expressed in the lung. Using a radiotracer technique, ASL volume and Cl(-) concentration ([Cl(-)]) were measured in cultured tracheal epithelia from normal and DeltaF508 -/- mice. The estimated ASL volume was similar for both groups. There were no differences in ASL [Cl(-)] in DeltaF508 -/- and normal mice (13.8 +/- 2.6 vs. 17.8 +/- 5.6 meq/l). Because ASL [Cl(-)] is low in normal and mutant mice, salt-sensitive antimicrobial factors, including MBD-1, may be normally active. (+info)Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins. (3/685)
beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two beta-defensins have been identified. Here, we report the identification of two genes encoding beta-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human beta-defensin-1 (HBD-1) gene and mouse beta-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat beta-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of beta-defensins. The beta-defensin genes mapped closely on rat chromosome 16 and were closely linked to the alpha-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were approximately 0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel beta-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of beta-defensins to host defense in the lung, kidney, and other tissues. (+info)Human beta-defensin-1 mRNA is transcribed in tympanic membrane and adjacent auditory canal epithelium. (4/685)
The external auditory canal is less susceptible to infections than the sensitive middle-ear cavity. Since recent research has provided insight to the production of potent antimicrobial peptides from various surface epithelia, we wanted to investigate whether protection of the external auditory canal in part could be explained by the production of human beta-defensin-1 (HBD-1). This particular peptide is known to be constitutively expressed in various surface epithelia, such as airway, skin, and urogenital tissues. By reverse transcriptase PCR we demonstrate HBD-1 mRNA in the pars tensa and pars flaccida of the tympanic membrane and in the meatal skin. In situ hybridization studies localized the HBD-1 mRNA to the epidermal layer of these tissues. The HBD-1 transcripts were also evident in the sebaceous glands and in hair follicles of the meatal skin. In contrast, HBD-1 mRNA was not detected in the tympanal epithelium of the eardrum. The widespread presence of mRNA encoding for this broad-spectrum antimicrobial peptide in the meatal skin and tympanic membrane suggests that HBD-1 participates in the innate antimicrobial defense of the external auditory canal and middle-ear cavity. (+info)Cloning and expression of bovine neutrophil beta-defensins. Biosynthetic profile during neutrophilic maturation and localization of mature peptide to novel cytoplasmic dense granules. (5/685)
beta-Defensins are microbicidal peptides implicated in host defense functions of phagocytic leukocytes and certain surface epithelial cells. Here we investigated the genetic structures and cellular expression of BNBD-4, -12, and -13, three prototypic bovine neutrophil beta-defensins. Characterization of the corresponding cDNAs indicated that BNBD-4 (41 residues) derives from a 63-amino acid prepropeptide and that BNBD-12 (38 residues) and BNBD-13 (42 residues) derive from a common 60-amino acid precursor (BNBD-12/13). The peptides were found to be encoded by two-exon genes that are closely related to bovine epithelial beta-defensin genes. BNBD-4 and BNBD-12/13 mRNAs were most abundant in bone marrow, but were expressed differentially in certain non-myeloid tissues. In situ hybridization and immunohistochemical studies demonstrated that BNBD-4 synthesis is completed early in myelopoiesis. BNBD-12 was localized exclusively to the novel dense granules, organelles that also contain precursors of cathelicidins, antimicrobial peptides that undergo proteolytic processing during phagocytosis. In contrast to cathelicidins, Western blot analyses revealed that mature beta-defensins are the predominant organellar form in myeloid cells. Stimulation of neutrophils with phorbol myristate acetate induced secretion of BNBD-12, indicating that it is co-secreted with pro-cathelicidins. The exocytosis of BNBD-12 by activated neutrophils reveals different mobilization pathways for myeloid alpha- and beta-defensins. (+info)Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. (6/685)
Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta-defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta-defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin. Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6. (+info)Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. (7/685)
The intestinal epithelium forms a physical barrier to limit access of enteric microbes to the host and contributes to innate host defense by producing effector molecules against luminal microbes. To further define the role of the intestinal epithelium in antimicrobial host defense, we analyzed the expression, regulation, and production of two antimicrobial peptides, human defensins hBD-1 and hBD-2, by human intestinal epithelial cells in vitro and in vivo. The human colon epithelial cell lines HT-29 and Caco-2 constitutively express hBD-1 mRNA and protein but not hBD-2. However, hBD-2 expression is rapidly induced by IL-1alpha stimulation or infection of those cells with enteroinvasive bacteria. Moreover, hBD-2 functions as a NF-kappaB target gene in the intestinal epithelium as blocking NF-kappaB activation inhibits the up-regulated expression of hBD-2 in response to IL-1alpha stimulation or bacterial infection. Caco-2 cells produce two hBD-1 isoforms and a hBD-2 peptide larger in size than previously described hBD-2 isoforms. Paralleling the in vitro findings, human fetal intestinal xenografts constitutively express hBD-1, but not hBD-2, and hBD-2 expression, but not hBD-1, is up-regulated in xenografts infected intraluminally with Salmonella. hBD-1 is expressed by the epithelium of normal human colon and small intestine, with a similar pattern of expression in inflamed colon. In contrast, there is little hBD-2 expression by the epithelium of normal colon, but abundant hBD-2 expression by the epithelium of inflamed colon. hBD-1 and hBD-2 may be integral components of epithelial innate immunity in the intestine, with each occupying a distinct functional niche in intestinal mucosal defense. (+info)Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. (8/685)
Human gingival epithelial cells (HGE) express two antimicrobial peptides of the beta-defensin family, human beta-defensin 1 (hBD-1) and hBD-2, as well as cytokines and chemokines that contribute to innate immunity. In the present study, the expression and transcriptional regulation of hBD-2 was examined. HBD-2 mRNA was induced by cell wall extract of Fusobacterium nucleatum, an oral commensal microorganism, but not by that of Porphyromonas gingivalis, a periodontal pathogen. HBD-2 mRNA was also induced by the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and phorbol myristate acetate (PMA), an epithelial cell activator. HBD-2 mRNA was also expressed in 14 of 15 noninflamed gingival tissue samples. HBD-2 peptide was detected by immunofluorescence in HGE stimulated with F. nucleatum cell wall, consistent with induction of the mRNA by this stimulant. Kinetic analysis indicates involvement of multiple distinct signaling pathways in the regulation of hBD-2 mRNA; TNF-alpha and F. nucleatum cell wall induced hBD-2 mRNA rapidly (2 to 4 h), while PMA stimulation was slower ( approximately 10 h). In contrast, each stimulant induced interleukin 8 (IL-8) within 1 h. The role of TNF-alpha as an intermediary in F. nucleatum signaling was ruled out by addition of anti-TNF-alpha that did not inhibit hBD-2 induction. However, inhibitor studies show that F. nucleatum stimulation of hBD-2 mRNA requires both new gene transcription and new protein synthesis. Bacterial lipopolysaccharides isolated from Escherichia coli and F. nucleatum were poor stimulants of hBD-2, although they up-regulated IL-8 mRNA. Collectively, our findings show inducible expression of hBD-2 mRNA via multiple pathways in HGE in a pattern that is distinct from that of IL-8 expression. We suggest that different aspects of innate immune responses are differentially regulated and that commensal organisms have a role in stimulating mucosal epithelial cells in maintaining the barrier that contributes to homeostasis and host defense. (+info)Beta-defensins are a family of small, cationic antimicrobial peptides that are produced by a variety of cells in the body, including immune cells, epithelial cells, and keratinocytes. They are part of the innate immune system and play a role in defending against bacterial, viral, and fungal infections. Beta-defensins are characterized by their beta-sheet structure, which gives them their name. They are typically 40-60 amino acids in length and have a net positive charge, which allows them to interact with negatively charged components of microbial membranes and disrupt their integrity. There are several different types of beta-defensins, including human beta-defensins 1-4 (hBD1-4), which are produced by epithelial cells and play a role in protecting the skin and mucous membranes from infection. Other types of beta-defensins, such as human beta-defensin 5 (hBD5) and human beta-defensin 6 (hBD6), are produced by immune cells and are involved in the immune response to infection. Beta-defensins have also been shown to have other functions in the body, including roles in wound healing, tissue repair, and regulation of the immune response. They have potential therapeutic applications in the treatment of a variety of conditions, including infections, inflammatory diseases, and cancer.
Defensins are a group of small, cationic peptides that are produced by various cells of the immune system, including neutrophils, macrophages, and epithelial cells. They are part of the innate immune system and play a crucial role in defending the body against infections caused by bacteria, viruses, fungi, and parasites. Defensins are characterized by their cysteine-rich, alpha-helical structure, which allows them to form stable complexes with negatively charged microbial membranes, leading to their disruption and killing. They also have anti-inflammatory and immunomodulatory properties, which help to regulate the immune response and prevent excessive tissue damage. Defensins are found in various body fluids, including saliva, tears, and sweat, as well as in the skin and mucous membranes. They are also present in the gut microbiome and have been shown to play a role in maintaining the balance of the gut microbiota. Defensins have been the subject of extensive research in the medical field due to their potential therapeutic applications in the treatment of various infectious and inflammatory diseases, including cystic fibrosis, inflammatory bowel disease, and cancer.
Alpha-defensins are a group of small, cationic peptides that are produced by various cells of the immune system, including neutrophils, monocytes, and epithelial cells. They are part of the innate immune system and play a role in defending the body against bacterial, fungal, and viral infections. Alpha-defensins are characterized by their alpha-helical structure and positive charge, which allows them to interact with negatively charged components of pathogens, such as lipopolysaccharides and peptidoglycans. They also have the ability to disrupt bacterial membranes and inhibit bacterial growth. In the medical field, alpha-defensins are being studied for their potential use as antimicrobial agents in the treatment of various infections, including those caused by multidrug-resistant bacteria. They are also being investigated as potential biomarkers for inflammatory and infectious diseases, as well as for their potential role in cancer and autoimmune disorders.
Beta defensin
Beta-defensin 3
Beta defensin 1
Beta-defensin 2
Defensin
DEFB119
Arthropod defensin
DEFB129
DEFB106A
DEFB104A
DEFB118
DEFB127
DEFB126
DEFB103A
Pulp (tooth)
Alpha defensin
Theta defensin
C-C chemokine receptor type 6
Virtual colony count
Ocular immune system
CCL20
Antimicrobial peptides
Airway basal cell
ELF4
Plant defensin
Cathelicidin
Perdita Barran
DEFB105A
Sperm-associated antigen 11B
Melanocortin
Defensin beta 3 Antikörper, ELISA Kits
BT-Laboratory - Beta defensin
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ELISA1
- The Eagle Biosciences beta Defensin-2 ELISA assay kit is intended for the quantification of Human BD-2 / beta Defensin-2 in serum, plasma, cell culture supernatants The beta Defensin-2 ELISA assay kit is for research use only and should not be used for diagnostic procedures. (eaglebio.com)
Proteins1
- The β-defensin proteins are expressed as the C-terminal portion of precursors, and are released by proteolytic cleavage of a signal sequence and, in some cases, a propeptide sequence. (peprotech.com)
Regulates2
- Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53. (antikoerper-online.de)
- In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered in cells overexpressing DEFB1, suggesting this to be one of the pathways by which defensin regulates IAV replication in HBEpCs. (cdc.gov)
Neutrophils3
- Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. (antikoerper-online.de)
- In cows, as many as 13 beta-defensins exist in neutrophils. (eaglebio.com)
- IL-17 confers protection by indirectly recruiting neutrophils and by working together with IL-22 to produce antimicrobial peptides and defensins. (virology.ws)
Peptides2
- Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulphide bonds. (eaglebio.com)
- Defensins (alpha and beta) are cationic peptides with a broad spectrum of antimicrobial activity that comprise an important arm of the innate immune system. (peprotech.com)
Cationic1
- The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic) regions interact with anionic phospholipid head groups and water. (eaglebio.com)
Antimicrobial Activity2
- This gene encodes defensin, beta 103B, which has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense. (antikoerper-online.de)
- Exploring Pleiotropic Functions of Canine β-Defensin 103: Nasal Cavity Expression, Antimicrobial Activity, and Melanocortin Receptor Activity. (antikoerper-online.de)
Human8
- An investigation of human beta-defensins and cathelicidin expression in patients with pterygium. (antikoerper-online.de)
- Gingival tissue human beta-defensin levels in relation to infection and inflammation. (bvsalud.org)
- To profile gingival tissue levels of human beta-defensin (hBD)-2 and hBD-3 in relation to gingival inflammation , Th17-related cytokine concentrations, Porphyromonas gingivalis counts, and gingipain and total protease activities. (bvsalud.org)
- The aim of this study was to evaluate the expression of human beta-defensin 2, tumour necrosis factor (TNF)-α and matrix metalloproteinase-2 in skin lesions of patients with hidradenitis suppurativa. (rsu.lv)
- Human beta-defensin 2 was negative in 12/14 specimens. (rsu.lv)
- Decreased human beta-defensin 2 in the presence of inflammatory (TNF-α-containing) cells suggests a decreased innate immunity in hidradenitis suppurativa-affected skin. (rsu.lv)
- 6. Dunsche A, Açil Y, Dommisch H, Siebert R, Schröder JM, Jepsen S. The novel human beta-defensin-3 is widely expressed in oral tissues. (bvsalud.org)
- Significant downregulation of beta-defensin1 gene (DEFB1) expression was observed when human bronchial epithelial cells (HBEpCs) were exposed to IAV. (cdc.gov)
Motif1
- β-defensins contain a six-cysteine motif that forms three intra-molecular disulfide bonds. (peprotech.com)
Sequence1
- Members of the defensin family are highly similar in protein sequence. (antikoerper-online.de)
Gene1
- Several mutations in the beta amyloid precursor gene cause autosomal dominant Alzheimer's Disease in a number of kindreds. (anaspec.com)
Bronchial1
- However, in other species, betadefensins are more often produced by epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract). (eaglebio.com)
Species1
- Every mammalian species explored thus far has beta-defensins. (eaglebio.com)
Alpha1
- On the basis of their size and pattern of disulphide bonding, mammalian defensins are classified into alpha, beta and theta categories. (eaglebio.com)
Source1
- defensin beta 4A [Source:HGNC S. (gsea-msigdb.org)
Products1
- Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. (eaglebio.com)
Mouse1
- Publication: Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs. (michael-nehls.de)
Activity1
- The antimicrobial peptide, beta-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. (cdc.gov)
Role1
- In conclusion, the reduction in IAV copy number in DEFB1 overexpressing cells suggests that beta-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development. (cdc.gov)
Epithelial cells2
- human, mouse or other beta β- and alpha α- defensins are expressed by neutrophils ( α- ), lymphocytes and epithelial cells. (b-defensin.com)
- DEFENSINS found mainly in epithelial cells. (nih.gov)
Locus2
Genes3
Proteins2
- Antimicrobial proteins in the cervicovaginal space, such as beta defensins, modulate immune responses to bacteria and have been shown to modulate the risk of sPTB from non-optimal microbiota. (nih.gov)
- In addition the role of mucins, thrombospondin, salivary soluble proteins, histatins, interferon, beta-defensins, secretory leukocyte protease inhibitor (SLPI) and other anti-microbial factors in control of HIV and opportunistic infections is needed. (nih.gov)
Characterization1
- 10. Characterization and functions of beta defensins in the epididymis. (nih.gov)
High3
- Objectives: Our objectives were to determine whether psychosocial stress was associated with a mediator of the immune system in the cervicovaginal space, beta defensin-2, and to examine the combined impact of high stress and low cervicovaginal beta defensin-2 levels on the odds of sPTB. (nih.gov)
- We modeled associations of high stress and low cervicovaginal beta defensin-2 levels using multivariable logistic regression. (nih.gov)
- defensin 1 and has high frequency in Africans and Afro-Americans. (cdc.gov)