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Last updated: 13
|DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children.|
AIDS. 2006 Aug 1;20(12):1673-5.
In our study we analysed three single nucleotide polymorphisms (SNPs) in the 5' untranslated region (UTR) of the DEFB1 gene, namely -52(G/A) -44(C/G) and -20(G/A), in three groups of northeastern Brazilian children in order to assess their role in HIV-1 infection. Our results allowed us to hypothesize that the SNPs located in the 5' UTR of the DEFB1 gene can be employed as a marker of risk for HIV-1 infection.
|alpha-Defensins 1, 2, and 3 are expressed by granulocytes in lymphoid tissues of HIV-1-seropositive and -seronegative individuals.|
J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):529-36
alpha-Defensins 1, 2, and 3 exert antiretroviral activity in vitro, but their role in controlling HIV-1 replication in vivo and the cells that produce them are controversial. This study sought to determine whether alpha-defensins are present in HIV-1-infected individuals' lymphoid tissues, the major site of HIV-1 replication, and to identify the cells that express them. alpha-Defensin expression was evaluated by immunostaining inguinal lymph node sections from 19 untreated HIV-1-infected individuals and 8 individuals at low risk or seronegative for HIV-1 infection. Percentages of tissue sections that stained positively for alpha-defensins were not significantly different between HIV-seropositive (median, 7.6%) and -seronegative (median, 5.5%) individuals. Conditions that could have produced lymph node inflammation were present in most seronegative subjects, and their lymph node weights correlated with alpha-defensin expression (Spearman rho = 0.833; P = 0.010). A median of 100% (range, 95%-100%) of alpha-defensin-expressing lymph node cells from 8 subjects coexpressed the granulocyte marker, CD15. CD15 and alpha-defensin staining correlated (Spearman rho = 0.622; P < 0.001). These data suggest that alpha-defensins within lymphoid tissue are expressed by granulocytes and are prevalent in HIV-1-seronegative individuals with inflammatory processes as well as HIV-1-infected individuals. The role of alpha-defensins in controlling HIV-1 replication merits further investigation.
|Pattern of mRNA expression of beta-defensins in basal cell carcinoma|
BMC Cancer. 2006 Jun 23;6:163
BACKGROUND: Although the human beta-defensins hBDs today seem to have diverse functional activities in innate antimicrobial immunity, a few reports also indicated an altered expression of these antimicrobial peptides (AMPs) in tissues of cancers such as oral squamous cell carcinoma. The present work was aimed on the study of hBD gene expression in basal cell carcinoma (BCC) which is the most common cancer in humans. METHODS: Twenty-two non-ulcerated BCCs (12 nodular type, 10 superficial type) have been analysed for the presence of hBD (1-3) mRNA by quantitative real-time RT-PCR. As controls, non-lesional skin specimens of BCC patients as well as samples of healthy subjects were assessed by RT-PCR. RESULTS: hBD-1 levels in healthy controls and non-lesional skin of BCC patients were significantly (P < 0.05) higher than the levels observed in tumour tissue. Moreover, BCCs showed significantly (P < 0.05) increased mRNA expression of hBD-2 as compared to controls. There was no significant (P > 0.05) difference between lesional mRNA levels for hBD-3 and those levels observed in controls. The mRNA expression of hBDs (1-3) found in nodular and superficial BCCs did not significantly (P > 0.05) differ. CONCLUSION: The gene expression patterns of hBD-1 and hBD-2 are for the first time shown to be significantly altered in non-ulcerated BCCs as compared to intra-individual and inter-individual controls, respectively. The present findings may indicate that beside the antimicrobial activity of AMPs, hBDs may also play a role in the pathogenesis of BCC. However, functional and immunohistological studies investigating hBDs in patients with BCC are needed to confirm our data.
|Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children.|
Genes Immun. 2006 Jan;7(1):59-64.
Human beta-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5'-untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5-18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles -20A and -52G (P = 0.041-0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P = 0.001) and for G-52A under both recessive and codominant models (P = 0.008 and 0.035). The recessive model covariate was also positive and significant (P = 0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05-2.57); P = 0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.
|High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis|
J Invest Dermatol. 2005 Dec;125(6):1163-73
Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. Microarray data were confirmed on a selected set of genes by quantitative PCR and at the protein level by immunohistochemistry. We found overexpression of many antimicrobial proteins in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis.
|Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis.|
J Negat Results Biomed. 2005 Dec 7;4:9
Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.
|Reduced Paneth cell alpha-defensins in ileal Crohn's disease|
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18129-34
The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of alpha-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.
|Expression of human beta-defensin-3 in gingival epithelia|
J Periodontal Res. 2005 Dec;40(6):474-81
OBJECTIVE: This study aimed to investigate the expression patterns of the newly discovered human beta-defensin-3 (hBD-3) in human gingiva. BACKGROUND: Human beta-defensins (hBDs) are a group of small, broad-spectrum, cationic antimicrobial peptides. Our recent study showed that the expression levels of hBD-1 and 2 peptides were associated with periodontal conditions. METHODS: A total of 49 gingival biopsies were collected, including 33 samples from 21 patients with chronic periodontitis and 16 samples from 16 periodontally healthy subjects. The expression of hBD-3 was detected by immunohistochemistry and in situ hybridization. Double staining was undertaken to identify hBD-3 peptide-positive cells, using CD-1a and cytokeratin 20 as markers for Langerhans cells and Merkel cells, respectively. RESULTS: hBD-3 peptide was detected in 88% of the samples, which was confined to the gingival epithelia. In healthy control subjects, hBD-3 peptide was more frequently detected in the basal layer as compared to the patients (53% vs. 18%, p < 0.05). In patients, hBD-3 expression extended from the basal layer to the spinous layers (82%), in which hBD-3 was confined to the basal and deep spinous layers in clinically healthy tissues from patients, whereas it extended to the superficial spinous layers in pocket tissues from patients (0% vs. 50%, p < 0.05). In both groups, hBD-3 peptide was expressed not only in gingival keratinocytes, but also in Langerhans cells and Merkel cells. hBD-3 transcripts were detected in 90% of the samples and they were confined to the basal and/or suprabasal layers of gingival epithelia. CONCLUSIONS: This study shows that hBD-3 is frequently expressed in gingival epithelia. The appropriate expression of hBD-3 peptide may contribute to the maintenance of periodontal homeostasis, possibly through its antimicrobial effect and promotion of adaptive immune responses.
|Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection|
Respir Res. 2005 Nov;6:130
BACKGROUND: Human beta-defensin-4 (hBD-4), a new member of the beta-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI) by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF). METHODS: The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA). Localization of hBD-4 was studied through immunohistochemical analysis (IHC). We investigated the effects of lipopolysaccharide (LPS) on hBD-4 expression and its release from small airway epithelial cells (SAEC). We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. RESULTS: hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. CONCLUSION: This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.
|Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens|
J Heart Lung Transplant. 2005 Aug;24(8):1055-66
BACKGROUND: Rejection and obliterative bronchiolitis are barriers to sustained graft function in recipients of transplanted lungs. Early detection is hindered by inadequate tests and an incomplete understanding of the molecular events preceding or accompanying graft deterioration. METHODS: Hypothesizing that genes involved in immune responses and tissue remodeling produce biomarkers of rejection, we measured the expression of 192 selected genes in 72 sets of biopsy specimens from human lung allografts. Gene transcripts were quantified using a 2-step, multiplex, real-time polymerase chain reaction approach in endobronchial and transbronchial biopsy specimens from transplant recipients without acute infections undergoing routine surveillance bronchoscopy. RESULTS: Comparisons of histopathology in parallel biopsy specimens identified 6 genes correlating with rejection as manifested by lymphocytic bronchitis, a suspected harbinger of obliterative bronchiolitis. For example, beta2-defensin and collagenase transcripts in inflamed bronchi increased 37-fold and 163-fold, respectively. By contrast, these transcripts did not correlate with acute rejection in transbronchial specimens. Further, no correspondence was noted between histopathologic bronchitis and parenchymal rejection when endobronchial and transbronchial samples were obtained from the same patient. CONCLUSIONS: Our highly sensitive method permits quantitation of many gene transcripts simultaneously in small, bronchoscopically acquired biopsy specimens of allografts. Transcript signatures obtained by this approach suggest that airway and alveolar responses to rejection differ and that endobronchial biopsy specimens assess lymphocytic bronchitis and chronic rejection but are not proxies for transbronchial biopsy specimens. Further, they reveal changes in airway expression of the specific genes involved in host defense and remodeling and suggest that the measurement of transcripts correlating with lymphocytic bronchitis may be diagnostic adjuncts to histopathology.