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1.
Br Poult Sci ; 61(4): 357-365, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32290685

RESUMO

1. Chicken salmonellosis is a common zoonotic infectious disease transmitted both vertically and horizontally. Avian beta-defensins (gallinacins) play an important role in the innate defence of the host and provide broad-spectrum immunity against multiple pathogens. 2. To detect the relationship between immune genes and salmonella carrier status and susceptibility to salmonellosis in chickens, polymorphisms with carrier-state susceptibility to salmonella and, hence, developing salmonellosis, were investigated in three avian beta-defensin genes (AvBD4, AvBD5, and AvBD14) in a Chinese local chicken breed, based on a case-control study. 3. Fifteen, twenty and nineteen SNPs were found in AvBD4, AvBD5 and AvBD14, respectively. Among the 54 total SNPs, four resulted in non-synonymous substitution of amino acid changes. Five SNPs in AvBD5 and four SNPs in AvBD14 were significantly associated with salmonellosis susceptibility (P < 0.05). Using the PHASE program, thirteen, ten and twelve major haplotypes were constructed in AvBD4, AvBD5 and AvBD14. Logistic regression analysis revealed that five haplotypes in AvBD5 and six haplotypes in AvBD14 were significantly associated with salmonellosis susceptibility, but no significant haplotype in AvBD4 was detected. A total of six strongly susceptible haplotypes with odds ratio (OR) values greater than 2.0 and four strongly resistant haplotypes with OR value less than 0.5 were revealed in the three genes examined. 4. These results suggested that the AvBD5 and AvBD14 genes may play an important role in the susceptibility to salmonellosis in chickens.


Assuntos
Salmonelose Animal , beta-Defensinas/genética , Animais , Estudos de Casos e Controles , Galinhas , Haplótipos , Polimorfismo de Nucleotídeo Único , Salmonella
2.
PLoS One ; 15(4): e0230231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240190

RESUMO

Enteroids are cultured primary intestinal epithelial cells that recapitulate epithelial lineage development allowing for a more complex and physiologically relevant model for scientific study. The large presence of intestinal stem cells (ISC) in these enteroids allows for the study of metabolite effects on cellular processes and resulting progeny cells. Short-chain fatty acids (SCFA) such as butyrate (BUT) are bacterial metabolites produced in the gastrointestinal tract that are considered to be beneficial to host cells. Therefore, the objective was to study the effects of SCFAs on biomarkers of ISC activity, differentiation, barrier function and epithelial defense in the intestine using mouse and human enteroid models. Enteroids were treated with two concentrations of acetate (ACET), propionate (PROP), or BUT for 24 h. Enteroids treated with BUT or PROP showed a decrease in proliferation via EdU uptake relative to the controls in both mouse and human models. Gene expression of Lgr5 was shown to decrease with BUT and PROP treatments, but increased with ACET. As a result of BUT and PROP treatments, there was an increase in differentiation markers for enterocyte, Paneth, goblet, and enteroendocrine cells. Gene expression of antimicrobial proteins Reg3ß, Reg3γ, and Defb1 were stimulated by BUT and PROP, but not by ACET which had a greater effect on expression of tight junction genes Cldn3 and Ocln in 3D enteroids. Similar results were obtained with human enteroids treated with 10 mM SCFAs and grown in either 3D or Transwell™ model cultures, although tight junctions were influenced by BUT and PROP, but not ACET in monolayer format. Furthermore, BUT and PROP treatments increased transepithelial electrical resistance after 24 h compared to ACET or control. Overall, individual SCFAs are potent stimulators of cellular gene expression, however, PROP and especially BUT show great efficacy for driving cell differentiation and gene expression.


Assuntos
Ácido Acético/farmacologia , Ácido Butírico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Propionatos/farmacologia , Esferoides Celulares/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Claudina-3/genética , Claudina-3/metabolismo , Enterócitos/citologia , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , Células Enteroendócrinas/citologia , Células Enteroendócrinas/efeitos dos fármacos , Células Enteroendócrinas/metabolismo , Células Caliciformes/citologia , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Humanos , Camundongos , Ocludina/genética , Ocludina/metabolismo , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Celulas de Paneth/citologia , Celulas de Paneth/efeitos dos fármacos , Celulas de Paneth/metabolismo , Cultura Primária de Células , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Junções Íntimas/efeitos dos fármacos , beta-Defensinas/genética , beta-Defensinas/metabolismo
3.
Genet Test Mol Biomarkers ; 24(3): 113-119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058800

RESUMO

Background: Human ß-defensin-2 is an antimicrobial peptide with antibiotic properties secreted by the oral cavity to protect the host against microbial attack. The inter-individual differences in defensin expression profiles due to genetic variation might be partly responsible for differences in disease susceptibility. Aims: The objective of this study was to examine whether variation in the human ß-defensin-2 gene (DEFB4A) is associated with chronic periodontitis (CP). Materials and Methods: This case-control study used Sanger sequencing to analyze two promoter polymorphisms of the DEFB4A gene with potential functional consequences using DNA samples collected from 200 unrelated individuals. Results: The DEFB4A rs1339258595 promoter polymorphism is associated with CP risk and clinical attachment level (CAL) but the rs3762040 polymorphism is not. Carriers of the T allele (rs1339258595) were approximately three times less likely to develop periodontitis compared with noncarriers (p = 0.0004, odds ratio = 0.35). Consistent with a protective role, the carriers of T allele had a lower CAL compared with the wild-type (G) allele. Moreover, the wild-type diplotype (GGGG) had a significantly higher risk of tooth loss compared with other diplotypes (p = 0.016). Conclusion: This study demonstrates that genetic variation in the promoter region of DEFB4A likely affects resistance to periodontal infection and might be a potential marker for CP risk and severity.


Assuntos
Periodontite Crônica/genética , beta-Defensinas/genética , Adulto , Alelos , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Turquia , beta-Defensinas/metabolismo
4.
J Agric Food Chem ; 68(9): 2648-2663, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32064872

RESUMO

Nutritional regulation of endogenous antimicrobial peptide (AMP) expression is considered a promising nonantibiotic approach to suppressing intestinal infection of pathogen. The current study investigated the effects of l-arginine on LPS-induced intestinal inflammation and barrier dysfunction in vivo and in vitro. The results revealed that l-arginine attenuated LPS-induced inflammatory response, inhibited the downregulation of tight junction proteins (TJP) (p < 0.05) by LPS, and maintained intestinal integrity. In porcine intestinal epithelial cells (IPEC-J2), l-arginine obviously suppressed (p < 0.05) the levels of IL-6 (220.63 ± 2.82), IL-8 (333.95 ± 3.75), IL-1ß (693.08 ± 2.38), and TNF-α (258.04 ± 4.14) induced by LPS. Furthermore, l-arginine diminished the LPS-induced expression of Toll-like receptor 4 (TLR4) and inhibited activation of TLR4-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Importantly, we proposed a new mechanism that l-arginine had the ability to stimulate the expression of porcine epithelial ß-defensins through activating the mammalian target of the rapamycin (mTOR) pathway, which exerts anti-inflammatory influence. Moreover, pBD-1 gene overexpression decreased (p < 0.05) the TNF-α level stimulated by LPS in IPEC-J2 cells (4.22 ± 1.64). The present study indicated that l-arginine enhanced disease resistance through inhibiting the TLR4/NF-κB and MAPK pathways and partially, possibly through increasing the intestinal ß-defensin expression.


Assuntos
Arginina/administração & dosagem , Intestinos/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Receptor 4 Toll-Like/imunologia , beta-Defensinas/genética , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , Suínos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , beta-Defensinas/imunologia
5.
J Agric Food Chem ; 68(6): 1621-1633, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31967468

RESUMO

Collagen peptides can promote wound healing and are closely related to microbiome colonization. We investigated the relationship among collagen peptides, wound healing, and wound microflora colonization by administering the murine wound model with Salmo salar skin collagen peptides (Ss-SCPs) and Tilapia nilotica skin collagen peptides (Tn-SCPs). We analyzed the vascular endothelial growth factor (VEGF), fibroblast growth factors (ß-FGF), pattern recognition receptor (NOD2), antimicrobial peptides (ß-defence14, BD14), proinflammatory (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines, macrophages, neutrophil infiltration levels, and microbial communities in the rat wound. The healing rates of the Ss-SCP- and Tn-SCP-treated groups were significantly accelerated, associated with decreased TNF-α, IL-6, and IL-8 and upregulated BD14, NOD2, IL-10, VEGF, and ß-FGF. Accelerated healing in the collagen peptide group shows that the wound microflora such as Leuconostoc, Enterococcus, and Bacillus have a positive effect on wound healing (P < 0.01). Other microbiome species such as Stenotrophomonas, Bradyrhizobium, Sphingomonas, and Phyllobacterium had a negative influence and decreased colonization (P < 0.01). Altogether, these studies show that collagen peptide could upregulate wound NOD2 and BD14, which were implicated in microflora colonization regulation in the wound tissue and promoted wound healing by controlling the inflammatory reaction and increasing wound angiogenesis and collagen deposition.


Assuntos
Colágeno/química , Proteínas de Peixes/química , Microbiota/efeitos dos fármacos , Proteína Adaptadora de Sinalização NOD2/genética , Peptídeos/administração & dosagem , Pele/química , Ferimentos e Lesões/fisiopatologia , beta-Defensinas/genética , Administração Cutânea , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Ciclídeos , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Masculino , Camundongos , Proteína Adaptadora de Sinalização NOD2/imunologia , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Salmo salar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologia , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/microbiologia , beta-Defensinas/imunologia
6.
Res Vet Sci ; 129: 28-38, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31927467

RESUMO

The ovine rumen is an immune interface with the external environment, participating in host defence responses. Ovine ruminal epithelial cells (ORECs) not only have a physical barrier function, but also secrete sheep ß-defensin-1 (SBD-1), which plays a key role in innate and adaptive immunity. Prebiotics are potential alternatives to infeed antibiotics. Saccharomyces cerevisiae cell wall (S.c.CW) is rich in prebiotics, which play roles in improving the growth performance of animals and regulating immunity. Here, we investigated whether S.c.CW induces SBD-1 expression in ORECs, as well as the underlying mechanism. The regulatory mechanisms of S.c.CW-induced up-regulation of SBD-1 were determined using quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blotting. S.c.CW significantly increased the expression of Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB), but had no effect on TLR4 expression. TLR2, MyD88, and NF-κB inhibition attenuated the induction of SBD-1 expression by S.c.CW. However, TLR4 inhibition only resulted in attenuated SBD-1 mRNA, having no effect on SBD-1 protein expression. Thus, we conclude that S.c.CW can induce SBD-1 expression and that this induction is regulated by the TLR2-MyD88-NF-κB pathway.


Assuntos
Regulação da Expressão Gênica , Probióticos/química , Saccharomyces cerevisiae/química , Ovinos/genética , beta-Defensinas/genética , Ração Animal , Animais , Parede Celular/fisiologia , Células Epiteliais/metabolismo , Rúmen/metabolismo , beta-Defensinas/metabolismo
7.
J Agric Food Chem ; 68(2): 512-522, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31870150

RESUMO

Host defense peptides (HDPs) are vital mucosal defense effectors of the innate immune response. The expression of HDPs is inducible in epithelial cells by potent endogenous inducers. Herein, our results demonstrate that sodium butyrate (NaB) induces the expression of porcine ß-defensin-3 (pBD3) and porcine epididymis protein 2 splicing variant C (pEP2C) in a dose- and time-dependent manner, without modifying the production of proinflammatory cytokines, in porcine intestinal epithelial cells (IPEC J2). Moreover, NaB promotes toll-like receptor 2 (TLR2) expression. TLR2 silencing inhibits the pBD3 and pEP2C expression induced by NaB but does not abolish the histone deacetylase (HDAC) inhibitory activity of NaB. We found that NaB activated the nuclear factor-κB (NF-κB) pathway. Importantly, the degree of cell confluence governs the regulatory responses but does not affect the HDAC activity of NaB. Furthermore, epidermal growth factor receptor (EGFR), but not the mitogen-activated protein kinase (MAPK) pathway, is vital during the NaB-induced pBD3 and pEP2C regulation process. We also demonstrated that pBD3 overexpression increases interleukin-18 levels. This study showed that NaB simultaneously induces pBD3 and pEP2C via TLR2 and EGFR in IPEC J2 cells without increasing the risk of a harmful inflammatory response.


Assuntos
Ácido Butírico/farmacologia , Receptores ErbB/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Receptor 2 Toll-Like/metabolismo , beta-Defensinas/metabolismo , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Receptores ErbB/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases/genética , Interleucina-18/genética , Interleucina-18/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Suínos , Receptor 2 Toll-Like/genética , beta-Defensinas/genética
8.
Proc Natl Acad Sci U S A ; 117(1): 337-345, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871151

RESUMO

Out of the 14 avian ß-defensins identified in the Gallus gallus genome, only 3 are present in the chicken egg, including the egg-specific avian ß-defensin 11 (Gga-AvBD11). Given its specific localization and its established antibacterial activity, Gga-AvBD11 appears to play a protective role in embryonic development. Gga-AvBD11 is an atypical double-sized defensin, predicted to possess 2 motifs related to ß-defensins and 6 disulfide bridges. The 3-dimensional NMR structure of the purified Gga-AvBD11 is a compact fold composed of 2 packed ß-defensin domains. This fold is the archetype of a structural family, dubbed herein as avian-double-ß-defensins (Av-DBD). We speculate that AvBD11 emanated from a monodomain gene ancestor and that similar events might have occurred in arthropods, leading to another structural family of less compact DBDs. We show that Gga-AvBD11 displays antimicrobial activities against gram-positive and gram-negative bacterial pathogens, the avian protozoan Eimeria tenella, and avian influenza virus. Gga-AvBD11 also shows cytotoxic and antiinvasive activities, suggesting that it may not only be involved in innate protection of the chicken embryo, but also in the (re)modeling of embryonic tissues. Finally, the contribution of either of the 2 Gga-AvBD11 domains to these biological activities was assessed, using chemically synthesized peptides. Our results point to a critical importance of the cationic N-terminal domain in mediating antibacterial, antiparasitic, and antiinvasive activities, with the C-terminal domain potentiating the 2 latter activities. Strikingly, antiviral activity in infected chicken cells, accompanied by marked cytotoxicity, requires the full-length protein.


Assuntos
Proteínas Aviárias/genética , Embrião de Galinha/imunologia , Galinhas/fisiologia , Desenvolvimento Embrionário/imunologia , beta-Defensinas/genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/ultraestrutura , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/veterinária , Bioensaio , Embrião de Galinha/crescimento & desenvolvimento , Embrião de Galinha/microbiologia , Embrião de Galinha/parasitologia , Coccidiose/imunologia , Coccidiose/parasitologia , Coccidiose/veterinária , Eimeria tenella/imunologia , Evolução Molecular , Genoma , Imunidade Inata/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Aviária/imunologia , Influenza Aviária/virologia , Ressonância Magnética Nuclear Biomolecular , Filogenia , Domínios Proteicos/genética , Domínios Proteicos/imunologia
9.
BMC Evol Biol ; 19(1): 214, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771505

RESUMO

BACKGROUND: The buffalo, despite its superior milk-producing ability, suffers from reproductive limitations that constrain its lifetime productivity. Male sub-fertility, manifested as low conception rates (CRs), is a major concern in buffaloes. The epididymal sperm surface-binding proteins which participate in the sperm surface remodelling (SSR) events affect the survival and performance of the spermatozoa in the female reproductive tract (FRT). A mutation in an epididymal secreted protein, beta-defensin 126 (DEFB-126/BD-126), a class-A beta-defensin (CA-BD), resulted in decreased CRs in human cohorts across the globe. To better understand the role of CA-BDs in buffalo reproduction, this study aimed to identify the BD genes for characterization of the selection pressure(s) acting on them, and to identify the most abundant CA-BD transcript in the buffalo male reproductive tract (MRT) for predicting its reproductive functional significance. RESULTS: Despite the low protein sequence homology with their orthologs, the CA-BDs have maintained the molecular framework and the structural core vital to their biological functions. Their coding-sequences in ruminants revealed evidence of pervasive purifying and episodic diversifying selection pressures. The buffalo CA-BD genes were expressed in the major reproductive and non-reproductive tissues exhibiting spatial variations. The Buffalo BD-129 (BuBD-129) was the most abundant and the longest CA-BD in the distal-MRT segments and was predicted to be heavily O-glycosylated. CONCLUSIONS: The maintenance of the structural core, despite the sequence divergence, indicated the conservation of the molecular functions of the CA-BDs. The expression of the buffalo CA-BDs in both the distal-MRT segments and non-reproductive tissues indicate the retention the primordial microbicidal activity, which was also predicted by in silico sequence analyses. However, the observed spatial variations in their expression across the MRT hint at their region-specific roles. Their comparison across mammalian species revealed a pattern in which the various CA-BDs appeared to follow dissimilar evolutionary paths. This pattern appears to maintain only the highly efficacious CA-BD alleles and diversify their functional repertoire in the ruminants. Our preliminary results and analyses indicated that BuBD-129 could be the functional ortholog of the primate DEFB-126. Further studies are warranted to assess its molecular functions to elucidate its role in immunity, reproduction and fertility.


Assuntos
Búfalos/genética , Búfalos/fisiologia , beta-Defensinas/genética , Animais , Simulação por Computador , Feminino , Fertilidade , Humanos , Masculino , Modelos Moleculares , Filogenia , Reprodução , Seleção Genética , Espermatozoides/metabolismo , beta-Defensinas/química , beta-Defensinas/metabolismo
10.
Commun Biol ; 2: 402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31701030

RESUMO

Human ß-defensins (hBD) play central roles in antimicrobial activities against various microorganisms and in immune-regulation. These peptides perturb phospholipid membranes for function, but it is not well understood how defensins approach, insert and finally disrupt membranes on the molecular level. Here we show that hBD-3 analogs interact with lipid bilayers through a conserved surface that is formed by two adjacent loops in the solution structure. By integrating a collection of 13C, 1H and 31P solid-state NMR methods with long-term molecular dynamic simulations, we reveal that membrane-binding rigidifies the peptide, enhances structural polymorphism, and promotes ß-strand conformation. The peptide colocalizes with negatively charged lipids, confines the headgroup motion, and deforms membrane into smaller, ellipsoidal vesicles. This study designates the residue-specific, membrane-bound topology of hBD-3 analogs, serves as the basis for further elucidating the function-relevant structure and dynamics of other defensins, and facilitates the development of defensin-mimetic antibiotics, antifungals, and anti-inflammatories.


Assuntos
beta-Defensinas/química , Sequência de Aminoácidos , Sítios de Ligação , Isótopos de Carbono/química , Humanos , Hidrogênio/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Isótopos de Nitrogênio/química , Ressonância Magnética Nuclear Biomolecular/métodos , Fosfatidilgliceróis/química , Ligação Proteica , Conformação Proteica em Folha beta , Estabilidade Proteica , beta-Defensinas/genética
11.
BMC Med Genet ; 20(1): 149, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477042

RESUMO

BACKGROUND: Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role in the pathogenesis of rotator cuff disease. Several genes are responsible for rotator cuff disease. The aim of this study was to perform a systematic review on genetic association between rotator cuff disease and genes variations. METHODS: A systematic review of the literature was performed, in accordance with the PRISMA guidelines. PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases were searched comprehensively using the keywords: "Rotator cuff", "Gene", "Genetic", "Predisposition", "Single-nucleotide polymorphism" and "Genome-wide association". RESULTS: 8 studies investigating genes variations associated with rotator cuff tears were included in this review. 6 studies were case-control studies on candidate genes and 2 studies were GWASs. A significant association between SNPs and rotator cuff disease was found for DEFB1, FGFR1, FGFR3, ESRRB, FGF10, MMP-1, TNC, FCRL3, SASH1, SAP30BP, rs71404070 located next to cadherin8. Contradictory results were reported for MMP-3. CONCLUSION: Further investigations are warranted to identify complete genetic profiles of rotator cuff disease and to clarify the complex interaction between genes, encoded proteins and environment. This may lead to individualized strategies for prevention and treatment of rotator cuff disease. LEVEL OF EVIDENCE: Level IV, Systematic Review.


Assuntos
Variação Genética , Estudo de Associação Genômica Ampla , Lesões do Manguito Rotador/genética , Caderinas/genética , Bases de Dados Factuais , Fator 10 de Crescimento de Fibroblastos/genética , Humanos , Metaloproteinase 1 da Matriz/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptores Estrogênicos/genética , Receptores Imunológicos/genética , Manguito Rotador , Tenascina/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , beta-Defensinas/genética
12.
J Dairy Sci ; 102(12): 11636-11651, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548051

RESUMO

The objective of this study was to evaluate expression of a cluster of genes encoding ß-defensin antimicrobial peptides in neutrophils of postpartum cows in relation to prepartum dietary cation-anion difference (DCAD), vitamin D, and postpartum disease. Pregnant dry Holstein cows (28 nulliparous and 51 parous) at 255 d gestation were blocked by parity and randomly assigned to 4 prepartum diets of positive (+130 mEq/kg) or negative (-130 mEq/kg) DCAD and either 3 mg vitamin D3 or 3 mg of 25-hydroxyvitamin D3 per 11 kg of dry matter/d. Treatment diets were fed from 255 d of gestation until calving. Peripheral blood neutrophils of 35 parous cows were collected at 0 and 3 d after calving and stimulated with 0 or 100 ng/mL of lipopolysaccharide (LPS). Furthermore, serum Ca and incidences of postpartum diseases were recorded for all cows. The mRNA transcripts of ß-defensin genes were quantified by real-time PCR, and data were analyzed with a general linear mixed model to test for fixed effects and interactions of day, level of DCAD, source of vitamin D, and incidence of disease. Effects of DCAD and vitamin D on neutrophil oxidative burst and phagocytosis were previously reported but were analyzed for effects of disease in the present study. Transcripts for DEFB1, DEFB3, DEFB4, DEFB5, DEFB7, DEFB10, and lingual antimicrobial peptide (LAP) in neutrophils were upregulated by LPS at 0 d but not at 3 d. Transcripts for DEFB4 and DEFB7 in LPS-stimulated neutrophils were greater in cows fed negative DCAD diets compared with positive DCAD. Source of vitamin D (vitamin D3 vs. 25-hydroxyvitamin D3) did not affect expression of ß-defensins in neutrophils. Cows with postpartum subclinical hypocalcemia (serum Ca <2.0 mM) had decreased DEFB3, DEFB4, DEFB6, DEFB7, DEFB10, and LAP expression in LPS-stimulated neutrophils compared with cows that did not experience subclinical hypocalcemia. Likewise, DEFB4, DEFB6, DEFB7, DEFB10, and LAP in LPS-stimulated neutrophils at 3 d postpartum were positively associated with serum Ca at 0 d postpartum. Transcripts for DEFB7, DEFB10 and LAP also were less abundant in neutrophils from cows with metritis compared with healthy cows. In conclusion, feeding a prepartum negative DCAD to improve postpartum serum Ca resulted in greater neutrophil ß-defensin expression, and greater neutrophil ß-defensin expression was positively associated with postpartum health.


Assuntos
Ração Animal/análise , Ânions/metabolismo , Cátions/metabolismo , Doenças dos Bovinos/metabolismo , Hipocalcemia/veterinária , beta-Defensinas/genética , Animais , Bovinos , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Regulação da Expressão Gênica , Humanos , Hipocalcemia/metabolismo , Lactação , Neutrófilos/metabolismo , Paridade , Período Pós-Parto , Gravidez , Distribuição Aleatória , Vitamina D/metabolismo
13.
BMC Genomics ; 20(1): 684, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470795

RESUMO

BACKGROUND: We report the sequencing, assembly and analysis of the genome of the Komodo dragon (Varanus komodoensis), the largest extant lizard, with a focus on antimicrobial host-defense peptides. The Komodo dragon diet includes carrion, and a complex milieu of bacteria, including potentially pathogenic strains, has been detected in the saliva of wild dragons. They appear to be unaffected, suggesting that dragons have robust defenses against infection. While little information is available regarding the molecular biology of reptile immunity, it is believed that innate immunity, which employs antimicrobial host-defense peptides including defensins and cathelicidins, plays a more prominent role in reptile immunity than it does in mammals. . RESULTS: High molecular weight genomic DNA was extracted from Komodo dragon blood cells. Subsequent sequencing and assembly of the genome from the collected DNA yielded a genome size of 1.6 Gb with 45x coverage, and the identification of 17,213 predicted genes. Through further analyses of the genome, we identified genes and gene-clusters corresponding to antimicrobial host-defense peptide genes. Multiple ß-defensin-related gene clusters were identified, as well as a cluster of potential Komodo dragon ovodefensin genes located in close proximity to a cluster of Komodo dragon ß-defensin genes. In addition to these defensins, multiple cathelicidin-like genes were also identified in the genome. Overall, 66 ß-defensin genes, six ovodefensin genes and three cathelicidin genes were identified in the Komodo dragon genome. CONCLUSIONS: Genes with important roles in host-defense and innate immunity were identified in this newly sequenced Komodo dragon genome, suggesting that these organisms have a robust innate immune system. Specifically, multiple Komodo antimicrobial peptide genes were identified. Importantly, many of the antimicrobial peptide genes were found in gene clusters. We found that these innate immunity genes are conserved among reptiles, and the organization is similar to that seen in other avian and reptilian species. Having the genome of this important squamate will allow researchers to learn more about reptilian gene families and will be a valuable resource for researchers studying the evolution and biology of the endangered Komodo dragon.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Imunidade Inata/genética , Lagartos/genética , beta-Defensinas/genética , Animais , Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/química , Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Lagartos/sangue , Lagartos/imunologia , Família Multigênica , beta-Defensinas/sangue , beta-Defensinas/química
14.
Vet Res Commun ; 43(4): 261-269, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407222

RESUMO

Toll like receptors (TLRs) and ß-defensins expressed in the endometrium are part of the innate uterine defense mechanism (UDM). In the present study, transcriptional profile of TLRs (1-3, 6-8, 10, and) and ß-defensins such as lingual antimicrobial peptide (LAP), tracheal antimicrobial peptide (TAP) and bovine neutrophil beta-defensin 4 (BNBD4) were studied. Bubaline genitalia were collected from abattoir and the endometrium was categorized into one of the following seven groups (n = 7/group) based on cyclicity and endometritis: follicular non-endometritis (FNE), luteal non-endometritis (LNE), follicular cytological endometritis (FCE), luteal cytological endometritis (LCE), follicular purulent endometritis (FPE), luteal purulent endometritis (LPE) and acyclic non-endometritis (ANE). Cytological endometritis (CE) was diagnosed by uterine cytology while purulent endometritis (PE) was diagnosed by the presence of purulent or mucopurulent exudate in the uterine lumen. Real time PCR was performed and the relative fold change was analysed. TLR1 and BNBD4 transcripts were not found in the buffalo endometrium. Of all the innate immune genes studied, upregulation of TLR and ß-defensins was mostly contributed by the inflammatory status of endometrium. Further, there was a prominent upregulation of TAP in buffaloes with endometritis. However, no association could be found between the inflammatory status of the endometrium and phase of estrous cycle with respect to the expression of TLRs and ß-defensins.


Assuntos
Búfalos , Endometrite/veterinária , Regulação da Expressão Gênica/imunologia , Receptores Toll-Like/genética , beta-Defensinas/genética , Animais , Endometrite/imunologia , Endométrio/imunologia , Feminino , Perfilação da Expressão Gênica , Reação em Cadeia da Polimerase em Tempo Real
15.
Pharmazie ; 74(7): 390-396, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288894

RESUMO

Previous studies showed that DEFB1 gene polymorphisms may impact the development and progression of periodontitis; nevertheless, inconsistent conclusions were described. This study meta-analytically explored the association between periodontitis the DEFB1 gene polymorphisms and periodontitis. We searched PubMed, Embase, Springer and Cochrane Library for the relevant case-control studies of periodontitis up to February 13th, 2019. Two reviewers selected studies according to the predefined inclusion and exclusion criteria. Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies, and the combined effect size was calculated using R 3.12 software. A total of 9 studies involving 4113 patients and 2373 controls were included. Meta-analysis of DEFB1-G1654A gene polymorphisms showed that there were significant differences in model A vs. G (OR = 3.7876, 95%CI = 2.9051-4.9382, P < 0.001), AA vs. GG (OR = 4.6743, 95%CI = 3.0900-7.0710, P < 0.001), AA vs.GG + AG (OR = 3.5131, 95%CI = 2.4496-5.0384, P < 0.001), AA + AG vs. GG (OR = 4.3087, 95%CI = 2.8827-6.4402, P < 0.001) and AG vs. GG (OR = 3.0639, 95%CI = 1.6804-5.5863, P = 0.003). However, no significant differences were found between DEFB1 rs11362, rs1799946 and rs1800972 and periodontitis. Sensitivity analysis implied that our results were robust and no publication bias was noticed. Our meta-analysis showed that the DEFB1-G1654A polymorphism may be a genetic susceptibility factor for periodontitis.


Assuntos
Predisposição Genética para Doença , Periodontite/genética , beta-Defensinas/genética , Humanos , Periodontite/epidemiologia , Periodontite/patologia , Polimorfismo de Nucleotídeo Único
16.
Gene ; 710: 218-232, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158448

RESUMO

Alterations in the global gene expression profile are considered to contribute to the various physiological and pathological changes during the course of ageing. Genes that code for the molecular components of the innate system are alter markedly as ageing occurs; and this may define the susceptibility of very young and very old individuals to reproductive tract infections. The expression pattern of genes that code for beta-defensins (effectors of innate immune response) in male reproductive tract tissues of different stages of ageing is not yet reported. Further, the induction of beta-defensins during endotoxin challenge and whether epigenetic modulators can influence the expression of these genes in different stages of ageing are not reported. We analyzed the basal mRNA levels of beta-defensins and defensin-like proteins (Sperm Associated Antigen 11 (SPAG11) family members), their induction during endotoxin challenge and modulation by epigenetic modifiers (Trichostatin A and Azacytidine) in the caput, cauda, testis, prostate and seminal vesicle of rats that represent early stage to late stages of life (20 day to 730 day old). We observed differential basal gene expression pattern in the male reproductive tract tissues and the induction by LPS was not consistent neither among the age groups not the tissues analyzed. Trichostatin A and Azacytidine also influenced antimicrobial gene expression and the pattern was not consistent in different tissues obtained from different age groups. Results of this study demonstrate that antimicrobial gene expression varies to a great extent during ageing and is strongly influenced by endotoxins and epigenetic modulators.


Assuntos
Envelhecimento/genética , Genitália Masculina/química , Glicopeptídeos/genética , beta-Defensinas/genética , Animais , Azacitidina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genitália Masculina/efeitos dos fármacos , Ácidos Hidroxâmicos/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Ratos , Ratos Wistar
17.
Arch Oral Biol ; 104: 141-149, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203191

RESUMO

OBJECTIVES: The aim of this meta-analysis was to analyze the association between periodontitis risk and gene polymorphisms of hBD-1 (rs11362, rs1799946 and rs1800972) and CD14 (rs2569190) by data synthesis. METHODS: This meta-analysis was performed using the PubMed and China National Knowledge Infrastructure databases and included 18 case-control studies. Statistical analyses were completed with Stata 12.0. RESULTS: In the overall analysis, there was no significant association between DEFB1 polymorphisms (rs11362, rs1799946 and rs1800972) and periodontitis risk. However, when examined by ethnicity, rs11362 (AG + AA vs GG: pooled OR = 3.561, 95% CI = 1.986-6.386, P = 0.000), rs1800972 (GC vs CC: pooled OR=0.391, 95% CI=0.216-0.708, P = 0.002; G vs C: pooled OR = 0.540, 95% CI = 0.337-0.867, P = 0.011) and rs1799946 (AG+AA vs GG: pooled OR=1.995, 95% CI=1.163-3.422, P = 0.012) polymorphisms were associated with periodontitis risk in Asian. Similarly, rs11362 and rs1799946 polymorphisms were related to periodontitis risk in Brazilian. In the stratified analysis by type of disease, rs1799946 polymorphism (AA vs GG: OR=1.444, 95% CI=1.051-1.983, P = 0.023; AG+AA vs GG: OR=1.374, 95% CI=1.021-1.849, P = 0.036; A vs G: OR=1.172, 95% CI=1.012-1.358, P = 0.034) and rs1800972 polymorphisms (GC vs CC: OR = 0.790, 95% CI = 0.638-0.979, P = 0.031; GG vs CC: OR=0.542, 95% CI=0.316-0.930, P = 0.026; GC+GG vs CC: OR=0.759, 95% CI=0.617-0.933, P = 0.009; G vs C: OR=0.773, 95% CI=0.649-0.921, P = 0.004) had significant associations with aggressive periodontitis (AP) risk. Nevertheless, in the overall and stratified analysis by the severity of periodontitis and ethnicity, no significant association was discovered between CD14 polymorphisms and periodontitis. CONCLUSIONS: This meta-analysis demonstrated that gene polymorphism of DEFB1 but not of CD14 might be involved in periodontitis risk.


Assuntos
Receptores de Lipopolissacarídeos , Periodontite , beta-Defensinas , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Receptores de Lipopolissacarídeos/genética , Periodontite/genética , Polimorfismo de Nucleotídeo Único , Risco , beta-Defensinas/genética
18.
Arch Oral Biol ; 101: 130-134, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30928860

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the possible association between two single nucleotide polymorphisms of the ß-defensin 1 gene: -20 G > A and -44 C > G at 5 untranslated region and recurrent aphthous stomatitis in a cohort of Polish patients. DESIGN: One hundred and six patients suffering from recurrent aphthous stomatitis and 96 healthy volunteers were genotyped at ß-defensin 1-20 G > A and -44 C > G using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The results were statistically analysed with the difference test between two proportion and chi-square tests with p < 0.05 as a significance level (Dell Statistica data analysis software system, version 13, Dell Inc. 2016). RESULTS: No statistically significant differences between the tested groups were revealed in the genotype distribution for -20 G > A and -44 C > G polymorphisms of the ß-defensin 1 gene. Stratification into carriers and non-carriers of alleles did not unequivocally show the single nucleotide polymorphism recognized as a risk factor for recurrent aphthous stomatitis. However, after gender stratification, statistically significant differences in the distribution of some DEFB1 genotypes were observed. Heterozygotes of G[-20]A and C[-44]G genotypes were found more frequently in males with RAS than in males from the control group. Moreover, a significantly higher rate of carriers of the polymorphic *A[-20] allele was found in males with RAS compared to the controls. CONCLUSIONS: The role of the tested single nucleotide polymorphisms of the ß-defensin 1 gene in the aetiology of recurrent aphthous stomatitis has not been confirmed. Further observations are required to clarify this potential association.


Assuntos
Regiões 5' não Traduzidas , Estomatite Aftosa/genética , beta-Defensinas/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polônia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(4): 371-375, 2019 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-30950029

RESUMO

OBJECTIVE: To investigate the association between the polymorphisms of 5'-UTR -52G/A (rs1799946), -44C/G (rs1800972), -20G/A (rs11362) in DEFB1 gene with chronic periodontitis in Henan Han population. METHODS: Peripheral blood genomic DNA of 436 patients with chronic periodontitis and 440 healthy controls were extracted and subjected to PCR-Sanger sequencing to determine the genotypes of DEFB1 5'-UTR -52G/A (rs1799946), -44C/G (rs1800972) and -20G/A (rs11362). The distribution of genotypes, allele frequencies and risk factors were analyzed by chi-square test and Logistic regression. RESULTS: There was no significant difference between healthy controls and chronic periodontitis in the genotype of -52G/A PCR- (rs1799946) and -20G/A (rs11362) (P> 0.05). While a significant difference was found between healthy controls and chronic periodontitis in -44C/G (rs1800972), the CC and CG genotype rate in the two groups were 64.5%, 82.1% and 28.2%, 14.4% respectively. One-way logistic analysis showed that the CG, GG genotype and allele G might be a protective factor. CONCLUSION: The DEFB1 -44C/G (rs1800972) is associated with chronic periodontitis in Henan Han population, and the -44CG, GG genotype and G allele may be the protective factors of chronic periodontitis in Henan Han population.


Assuntos
Periodontite Crônica , Polimorfismo Genético , beta-Defensinas/genética , Alelos , Estudos de Casos e Controles , Periodontite Crônica/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos
20.
J Dairy Sci ; 102(6): 5706-5712, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954263

RESUMO

Antimicrobial peptides are a common defense against bacterial infections in many species and a significant part of the innate immune response of the bovine mammary gland. The objective of this study was to investigate the influence of epigenetic factors on vitamin D and toll-like receptor-mediated induction of ß-defensins in mammary epithelial cells. Primary bovine mammary epithelial cells were treated with lipopolysaccharide (LPS, 0 or 100 ng/mL), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, 0 or 10 nM], and 5-aza-2'-deoxycytidine (5-Aza, inhibitor of DNA methyltransferase, 0 or 5 µM) or trichostatin A (TSA, inhibitor of histone deacetylase, 0 or 80 nM) in a factorial arrangement. Effects of treatments on ß-defensin gene expression along with genes for cytokines and enzymes known to be induced by LPS or 1,25(OH)2D3 were evaluated by quantitative PCR. The LPS treatment induced expression of ß-defensin (DEFB)3, DEFB5, DEFB7, DEFB10, enteric ß-defensin (EBD), lingual antimicrobial peptide (LAP), and tracheal antimicrobial peptide (TAP); whereas, the 1,25(OH)2D3 treatment increased DEFB5 and DEFB7 expression and decreased LAP. The 5-Aza treatment increased expression of DEFB3, DEFB5, DEFB10, EBD, LAP, and TAP in the presence and absence of LPS. The TSA treatment increased expression of DEFB3, DEFB4, DEFB5, DEFB7, and DEFB10 in the absence of LPS but decreased LPS-induced expression of and LAP and TAP. Together these results indicate that ß-defensin expression in bovine mammary epithelial cells is likely influenced by DNA methylation and histone acetylation. Investigation of environmental and nutritional factors that influence epigenetic control of ß-defensins in the mammary gland may be beneficial for improving resistance to intramammary infections.


Assuntos
Bovinos/metabolismo , Células Epiteliais/metabolismo , Histona Desacetilases/metabolismo , Lipopolissacarídeos/metabolismo , Glândulas Mamárias Animais/metabolismo , Metiltransferases/metabolismo , Vitamina D/análogos & derivados , beta-Defensinas/genética , Animais , Bovinos/genética , Metilação de DNA , Feminino , Histona Desacetilases/genética , Glândulas Mamárias Animais/citologia , Metiltransferases/genética , Vitamina D/metabolismo , beta-Defensinas/metabolismo
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