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1.
APMIS ; 128(1): 10-19, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642122

RESUMO

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL-10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte-derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7-ketocholesterol (7-kCH) - harmful oxidized form of cholesterol. The effect of E. coli LPS, 7-kCH and ApoB100 on the barrier functions of HUVECs in real-time cell electric impedance sensing system (RTCA-DP) was assessed. Furthermore, the effect of 7-kCH and ApoB100 on barrier functions of HUVECs co-cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7-kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL-10 mRNA expression. In HUVECs co-cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7-kCH, IL-10 mRNA expression was lower. E. coli LPS-exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100.


Assuntos
Células Dendríticas/efeitos dos fármacos , Escherichia coli/imunologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Interleucina-10/genética , Lipopolissacarídeos/imunologia , Junções Íntimas/efeitos dos fármacos , Apolipoproteína B-100/farmacologia , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/imunologia , Escherichia coli/química , Humanos , Cetocolesteróis/farmacologia , Lipopolissacarídeos/farmacologia , Ocludina/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/genética
2.
Pol J Microbiol ; 68(4): 457-464, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880890

RESUMO

Unravelling of the interplay between the immune system and non-diphtheria corynebacteria would contribute to understanding their increasing role as medically important microorganisms. We aimed at the analysis of pro- (TNF, IL-1ß, IL-6, IL-8, and IL-12p70) and anti-inflammatory (IL-10) cytokines produced by Jurkat T cells in response to planktonic and biofilm Corynebacterium amycolatum. Two reference strains: C. amycolatum ATCC 700207 (R-CA), Staphylococcus aureus ATCC 25923 (R-SA), and ten clinical strains of C. amycolatum (C-CA) were used in the study. Jurkat T cells were stimulated in vitro by the planktonic-conditioned medium (PCM) and biofilm-conditioned medium (BCM) derived from the relevant cultures of the strains tested. The cytokine concentrations were determined in the cell culture supernatants using the flow cytometry. The levels of the cytokines analyzed were lower after stimulation with the BCM when compared to the PCM derived from the cultures of C-CA; statistical significance (p < 0.05) was observed for IL-1ß, IL-12 p70, and IL-10. Similarly, planktonic R-CA and R-SA stimulated a higher cytokine production than their biofilm counterparts. The highest levels of pro-inflammatory IL-8, IL-1ß, and IL-12p70 were observed after stimulation with planktonic R-SA whereas the strongest stimulation of anti-inflammatory IL-10 was noted for the BCM derived from the mixed culture of both reference species. Our results are indicative of weaker immunostimulatory properties of the biofilm C. amycolatum compared to its planktonic form. It may play a role in the persistence of biofilm-related infections. The extent of the cytokine response can be dependent on the inherent virulence of the infecting microorganism.Unravelling of the interplay between the immune system and non-diphtheria corynebacteria would contribute to understanding their increasing role as medically important microorganisms. We aimed at the analysis of pro- (TNF, IL-1ß, IL-6, IL-8, and IL-12p70) and anti-inflammatory (IL-10) cytokines produced by Jurkat T cells in response to planktonic and biofilm Corynebacterium amycolatum. Two reference strains: C. amycolatum ATCC 700207 (R-CA), Staphylococcus aureus ATCC 25923 (R-SA), and ten clinical strains of C. amycolatum (C-CA) were used in the study. Jurkat T cells were stimulated in vitro by the planktonic-conditioned medium (PCM) and biofilm-conditioned medium (BCM) derived from the relevant cultures of the strains tested. The cytokine concentrations were determined in the cell culture supernatants using the flow cytometry. The levels of the cytokines analyzed were lower after stimulation with the BCM when compared to the PCM derived from the cultures of C-CA; statistical significance (p < 0.05) was observed for IL-1ß, IL-12 p70, and IL-10. Similarly, planktonic R-CA and R-SA stimulated a higher cytokine production than their biofilm counterparts. The highest levels of pro-inflammatory IL-8, IL-1ß, and IL-12p70 were observed after stimulation with planktonic R-SA whereas the strongest stimulation of anti-inflammatory IL-10 was noted for the BCM derived from the mixed culture of both reference species. Our results are indicative of weaker immunostimulatory properties of the biofilm C. amycolatum compared to its planktonic form. It may play a role in the persistence of biofilm-related infections. The extent of the cytokine response can be dependent on the inherent virulence of the infecting microorganism.


Assuntos
Biofilmes , Infecções por Corynebacterium/imunologia , Corynebacterium/fisiologia , Citocinas/imunologia , Linfócitos T/imunologia , Linhagem Celular , Corynebacterium/genética , Corynebacterium/imunologia , Infecções por Corynebacterium/genética , Infecções por Corynebacterium/microbiologia , Citocinas/genética , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Plâncton/genética , Plâncton/fisiologia
3.
Georgian Med News ; (294): 68-71, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687952

RESUMO

The aim of our work was to determine the gene polymorphism of cytokines IL-1ß (-511) and IL-10 (-1082) in children with nephrotic syndrome. 20 patients with nephrotic syndrome were recruited into the study from 2017 to 2018 years in single center. Our study included children with levels of glomerular filtration rate >90 ml/min. Genetic polymorphism of IL-1ß (-511) and IL-10 (-1082) and serum IL1ß were evaluated. Analyzing the contents of IL-1ß in serum of children with nephrotic syndrome, we found that IL-1ß was significantly increased in children with steroid-resistant nephrotic syndrome and with progression of glomerulonephritis compared with remission and with healthy children (p<0.05). The presence of C/T genotype is associated with increased production of interleukin-1ß in serum, compared with children with genotype C/C (p<0.05). Checking the polymorphism of SNP -1082 of IL-10 we determined that in 50% of children with nephrotic syndrome there was G/A genotype, in 40% - G/G genotype, and genotype А/А was only in 10% of patients. A strong direct relationship between the level of IL-1ß in serum and C/T allelic polymorphism of the gene IL-1ß (-511) was found (r=+0,56) (p<0.05). Gene polymorphism of IL-1ß (-511) can be used as a marker of progression of glomerulonephritis, nephrotic syndrome but more studies are needed.


Assuntos
Interleucina-10/genética , Interleucina-1beta/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Polimorfismo Genético/genética , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Masculino , Síndrome Nefrótica/imunologia
4.
Arq Gastroenterol ; 56(3): 323-328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633733

RESUMO

BACKGROUND: There has been little evidence to suggest that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms are significantly associated with susceptibility to celiac disease. Thus, we performed the present meta-analysis to explore the potential association between these polymorphisms and celiac disease risk. METHODS: Eligible studies were searched in PubMed, Medline, Embase, Web of Science and CNKI database up to April 20, 2019. Odds ratios with 95% confidence interval were calculated to assess the potential associations. Moreover, we performed the heterogeneity, sensitivity, and publication bias tests to clarify and validate the pooled results. RESULTS: Overall, nine case-control studies involving five studies with 737 cases and 1,338 control on IL-6 -174G>C polymorphism and four studies with 923 cases and 864 controls on IL-10 -1082A>G polymorphism were selected. The pooled ORs showed that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms were not significantly associated with increased risk of celiac disease under all five genetic models. There was no publication bias. CONCLUSION: To the best of our knowledge, this is the first meta-analysis summarizing all of the available studies on the association of IL-6 -174G>C and IL-10 -1082A>G polymorphisms with celiac disease. Our results suggest that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms may not be associated with increased risk of celiac disease. Moreover, large and well-designed studies are needed to fully describe the association of IL-6 -174G>C and IL-10 -1082A>G polymorphisms with celiac disease.


Assuntos
Doença Celíaca/genética , Predisposição Genética para Doença , Interleucina-10/genética , Interleucina-6/genética , Polimorfismo Genético , Estudos de Casos e Controles , Genótipo , Humanos , Metanálise como Assunto , Razão de Chances
5.
Medicine (Baltimore) ; 98(40): e17113, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577700

RESUMO

BACKGROUND: Periodontitis is a common disease with an unclear pathological mechanism. No precise consensus has been reached to evaluate the association between the IL-10 rs1800872 (- 592, -590, -597 C>A) polymorphism and periodontal disease. Thus, we performed this meta-analysis to collect more evidence-based information. METHODS: Four online databases, PubMed, Embase, Web of Science, and China Biology Medicine disc (CBM), were searched in August 2018. An odds ratio (OR) with a 95% confidence interval (CI) was applied to evaluate the association of the rs1800872 with periodontitis susceptibility. RESULTS: Twenty three case-control studies with 2714 patients and 2373 healthy controls were evaluated. The overall analyses verified that the IL-10 rs1800872 polymorphism was significantly associated with an increased risk of periodontitis in the allelic model, homozygote model, dominant model, and recessive model (A vs C: OR = 1.28, 95%CI = 1.11-1.49, P = .00, I = 56.87%; AA vs CC: OR = 2.06, 95%CI = 1.32-3.23, P = .00, I = 73.3%; AA + AC vs CC: OR = 1.42, 95%CI = 1.03-1.96, P = .03, I = 76.2%; AA vs AC + CC: OR = 1.78, 95%CI = 1.26-2.56, P = .00, I = 76.7%). Moreover, the subgroup analysis based on ethnicity, periodontitis type, and smoking status showed significant differences. CONCLUSIONS: The results of our meta-analysis demonstrate that rs1800872 is associated with periodontitis susceptibility in Caucasians and Asians. Moreover, A allele, AA genotype, CC genotype may be closely associated with chronic periodontitis (CP), while A allele, AA genotype may be closely associated with aggressive periodontitis (AgP).


Assuntos
Interleucina-10/genética , Periodontite/etnologia , Periodontite/genética , Periodontite Agressiva/etnologia , Periodontite Agressiva/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Periodontite Crônica/etnologia , Periodontite Crônica/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/etnologia
6.
Vet Immunol Immunopathol ; 216: 109912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446208

RESUMO

Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies.


Assuntos
Quimiocina CCL2/metabolismo , Doenças do Cão/terapia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-10/metabolismo , Melanoma/veterinária , Células Supressoras Mieloides/fisiologia , Animais , Quimiocina CCL2/genética , Doenças do Cão/metabolismo , Cães , Feminino , Gangliosídeos/administração & dosagem , Gangliosídeos/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Imunoterapia , Interleucina-10/genética , Masculino , Melanoma/terapia
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 789-795, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31416504

RESUMO

OBJECTIVE: To study the association of interleukin-10 (IL-10) -1082A/G, -819C/T, and -592C/A polymorphisms with IL-10 level and the severity of enterovirus 71 (EV71) infection in children. METHODS: A total of 137 children with hand-foot-mouth disease due to EV71 infection were enrolled as EV71 infection group, which was further divided into mild group with 91 children and severe group with 46 children, and 122 healthy children who underwent physical examination were enrolled as healthy control group. Related clinical data were collected. ELISA was used to measure the serum level of IL-10, and polymerase chain reaction-restriction fragment length polymorphism was used to analyze IL-10 -1082A/G, -819C/T and -592C/A polymorphisms. RESULTS: Compared with the healthy control group, the children with EV71 infection had significantly higher frequency of -1082 AA genotype and A allele (P<0.05). Among the children with EV71 infection, the severe group had significantly higher frequency of -1082 AA genotype and A allele than the mild group (P<0.05), while there was no significant difference in the distribution of IL-10 -819C/T and IL-10 -592C/A polymorphisms between the two groups (P>0.05). The severe group had a significantly higher serum level of IL-10 than the mild group and the healthy control group. IL-10 -1082 AA genotype, -819 TT genotype, and -592 AA genotype were associated with the low expression of IL-10 (P<0.05). As for haplotype, the EV71 infection group had a significantly lower frequency of GCC haplotype than the healthy control group (P<0.05). In the severe group, the children with ATA haplotype had a significantly lower IL-10 level than those with other haplotypes, and the children with GCC haplotype had a significantly higher IL-10 level than those with other haplotypes (P<0.05). There was no significant difference in IL-10 level between children with different haplotypes in the mild group and the healthy control group (P>0.05). CONCLUSIONS: IL-10 gene polymorphisms are associated with IL-10 expression and the severity of EV71 infection in children.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Interleucina-10/genética , Criança , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
8.
Parasitol Res ; 118(9): 2705-2713, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359134

RESUMO

Artemisinin, extracted from a medicinal herb Artemisia annua, is widely used to treat malaria and has shown potent anticancer activity. Artemisinin has been found to be effective against experimental visceral and cutaneous leishmaniasis. Despite extensive research to understand the complex mechanism of resistance to artemisinin, several questions remain unanswered. The artesunate (ART)-resistant line of Leishmania donovani was selected and cellular mechanisms associated with resistance to artemisinin were investigated. ART-resistant (AS-R) parasites showed reduced susceptibility towards ART both at promastigote and amastigote stage compared with ART sensitive (WT) parasites. WT and AS-R parasites were both more susceptible to ART at the early log phase of growth compared with late log phase. AS-R parasites were more infective to the host macrophages (p < 0.05). Evaluation of parasites' tolerance towards host microbicidal mechanisms revealed that AS-R parasites were more tolerant to complement-mediated lysis and nitrosative stress. ROS levels were modulated in presence of ART in AS-R parasites infected macrophages. Interestingly, infection of macrophages by AS-R parasites led to modulated levels of host interleukins, IL-2 and IL-10, in addition to nitric oxide. Additionally, AS-R parasites showed upregulated expression of genes of unfolded protein response pathway including methyltransferase domain-containing protein (HSP40) and flagellar attachment zone protein (prefoldin), that are reported to be associated with ART resistance in Plasmodium falciparum malaria. This study presents in vitro model of artemisinin-resistant Leishmania parasite and cellular mechanisms associated with ART resistance in Leishmania.


Assuntos
Antiprotozoários/administração & dosagem , Artemisininas/administração & dosagem , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Extratos Vegetais/administração & dosagem , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Artemisia annua/química , Artesunato/administração & dosagem , Feminino , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/imunologia , Interações Hospedeiro-Parasita , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Leishmania donovani/crescimento & desenvolvimento , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/fisiopatologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C
9.
Vet Microbiol ; 233: 124-132, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176398

RESUMO

Leptospirosis is a zoonosis, caused by pathogenic spirochetes of the genus Leptospira. Although cattle are usually the maintenance hosts of serovar Hardjo, Pomona is the most frequent serovar circulating in Argentina. The understanding of bovine innate immune response and the virulence of this serovar is important for future control measures. This work compares infection of bovine macrophages with the virulent L. interrogans sv Pomona strain AKRFB (P1) and its attenuated counterpart (P19). First, we confirmed attenuation in the hamster model. Mortality and lung hemorrhages occurred after P1 inoculation, while the survival rate was 100% in P19-infected animals. Cells infected with both strains showed statistically upregulated gene expression of pro-inflammatory cytokines, IL-1ß, IL-6 and TNFα. The level of expression of anti-inflammatory cytokine IL-10 was statistically different between strains. Increased expression of IL-10 was observed only in P1-infected cells. For the first time, we describe macrophages extracellular traps induced by infection of bovine macrophages (bMETs) with both, the virulent and attenuated Leptospira interrogans Pomona strains. P1 was found higher internalized when the phagocytosis was inhibited, suggesting a cell entrance of this strain also by an independent-phagocytosis pathway. Furthermore, P1 was higher colocalized with acidic and late endosomal compartments compared with P19. This data emphasizes the importance to deepen in Leptospira bovine macrophages particular invasion mechanisms and, furthermore, underline the value of studying the main hosts.


Assuntos
Imunidade Inata , Leptospira interrogans serovar pomona/patogenicidade , Macrófagos/imunologia , Macrófagos/microbiologia , Animais , Argentina , Bovinos , Células Cultivadas , Cricetinae , Citocinas/genética , Citocinas/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Leptospirose/imunologia , Pulmão/microbiologia , Pulmão/patologia , Sorogrupo , Virulência
10.
Acta Virol ; 63(2): 186-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230447

RESUMO

Little is known about the role of genetic variation in the genes for cytokines and susceptibility to viral infection especially torque teno virus (TTV) following allogeneic hematopoietic stem cell transplantation. In this study, the association between interleukin-12, interleukin-17, interleukin-10 (IL-12,-17,-10) and tumor necrosis factor-α (TNF-α) polymorphisms was evaluated in patients with TTV infection who underwent allogeneic hematopoietic stem cell transplantation from South of Iran. The single nucleotide polymorphisms in the cytokine genes including IL-12 (-1188A/C), IL-17 (-197G/A), IL-10 (-1082G/A, -819C/T and -592C/A) and TNF-α (-308 G/A) were analyzed by PCR-RFLP methods. While our results did not show any association between IL-17, IL-12 and IL-10 (-819C/T and -1082G/A) polymorphisms and TTV infection status, heterozygote genotype of IL-10 (-592C/A) had direct correlation with TTV infection and A allele of TNF-α (-308G/A) showed a protective effect against TTV infection (P = 0.05 and P = 0.025, respectively). Within the group of patients who experienced acute graft-versus-host disease, the AA genotype and the A allele of IL-17 (-197 G/A) were significantly higher in non-infected patients compared to infected ones (P = 0.024 and P = 0.057, respectively). It was also observed that among infected patients, the GG genotype of IL-17 and AA genotype of TNF-α were significantly increased in hematopoietic stem cell transplanted patients with low grade (grade I+II) acute graft-versus-host disease compared to high grade (grade III and IV) disease (P = 0.056 and P = 0.056, respectively). Taken together, genetic variation of IL-10 (-592C/A) and TNF-α (-308G/A) genes might be associated with susceptibility to TTV infection post hematopoietic stem cell transplantation. Keywords: TNF-α; interleukins; torque teno virus (TTV); hematopoietic stem cell transplantation (HSCT); graft versus host disease (GvHD).


Assuntos
Citocinas , Infecções por Vírus de DNA , Transplante de Células-Tronco Hematopoéticas , Torque teno virus , Citocinas/genética , Infecções por Vírus de DNA/genética , Humanos , Interleucina-10/genética , Interleucina-12/genética , Interleucina-17/genética , Irã (Geográfico) , Fator de Necrose Tumoral alfa/genética
11.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180043

RESUMO

In this study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using the extract of Hyssops officinalis L. via green method and confirmed by transmission electron microscopy, field emission scanning electron microscopy, X-ray powder diffraction and Fourier transforms infrared spectroscopy techniques. In the in vivo section, the anti-angiogenesis and antiinflammatory properties of the NPs were evaluated by the chorioallantoic membrane (CAM) assay and mouse paw edema test (induced by carrageenan), respectively. In the in vitro section, changes in the expression of angiogenesis genes (VEGF and VEGFR) and inflammatory genes (IL-1B and IL-10) were investigated by real-time quantitative polymerase chain reaction technique. In order to evaluate the cytotoxicity of ZnO-NPs, 3-5, 4-dimethylthiazol-2-yl) -5, 2-tetrazolium bromide (MTT) test was used on MDA-MB231 breast adenocarcinoma cell line. The results of the CAM assay showed that the ZnO-NPs significantly reduced the number and length of blood vessels, as well as the size and weight of the embryos. Evaluation of mouse paw edema showed that the NPs are able to decrease inflammation. Changes in the expression pattern of VEGF and VEGFR genes in MCF7 cells showed that the NPs have inhibitory effect on the expression of both genes. Expression levels of IL-10 and IL-1B genes also increased and decreased, respectively. The MTT test showed that the NP have the ability to decrease breast cancer cells. In conclusion, our results confirm that the ZnO-NPs synthesized by green method have promising anti-cancer properties.


Assuntos
Inibidores da Angiogênese/síntese química , Anti-Inflamatórios/síntese química , Citotoxinas/síntese química , Edema/tratamento farmacológico , Hyssopus/química , Nanopartículas/administração & dosagem , Óxido de Zinco/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Carragenina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Citotoxinas/farmacologia , Edema/induzido quimicamente , Edema/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Química Verde , Membro Posterior , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Células MCF-7 , Camundongos , Nanopartículas/química , Extratos Vegetais/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Óxido de Zinco/química
12.
Eur J Med Chem ; 177: 457-466, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31181405

RESUMO

Histone deacetylases (HDACs) play an important role in cancer, degenerative diseases and inflammation. The currently applied HDAC inhibitors in the clinic lack selectivity among HDAC isoforms, which limits their application for novel indications such as inflammatory diseases. Recent, literature indicates that HDAC 3 plays an important role among class I HDACs in gene expression in inflammation. In this perspective, the development and understanding of inhibitory selectivity among HDACs 1, 2 and 3 and their respective influence on gene expression need to be characterized to facilitate drug discovery. Towards this aim, we synthesized nine structural analogues of the class I HDAC inhibitor Entinostat and investigated their selectivity profile among HDACs 1, 2 and 3. We found that we can explain the observed structure activity relationships by small structural and conformational differences between HDAC 1 and HDAC 3 in the 'lid' interacting region. Cell-based studies indicated, however, that application of inhibitors with improved HDAC 3 selectivity did not provide an anti-inflammatory response in contrast to expectations from biochemical evidence in literature. Altogether, in this study, we identified structure activity relationships among class I HDACs and we connected isoform selectivity among class I HDACs with pro- and anti-inflammatory gene transcription in macrophages.


Assuntos
Anilidas/farmacologia , Benzamidas/farmacologia , Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Macrófagos/efeitos dos fármacos , Anilidas/síntese química , Anilidas/química , Anilidas/metabolismo , Animais , Benzamidas/síntese química , Benzamidas/química , Benzamidas/metabolismo , Domínio Catalítico , Histona Desacetilase 1/química , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/metabolismo , Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Inflamação/genética , Interleucina-10/genética , Interleucina-6/genética , Camundongos , Simulação de Acoplamento Molecular , Subunidade p50 de NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Ligação Proteica , Células RAW 264.7 , Estereoisomerismo , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/genética
13.
Virol J ; 16(1): 79, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196204

RESUMO

BACKGROUND: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population. METHODS: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1ß, IL-17, IL-10 and IL-28 genes. RESULTS: The frequencies of the IL-1ß rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008). CONCLUSIONS: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.


Assuntos
Citocinas/genética , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Citocinas/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza B , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Rev Soc Bras Med Trop ; 52: e20180481, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31166487

RESUMO

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.


Assuntos
Infecções por HTLV-I/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Bexiga Urinária Hiperativa/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Bexiga Urinária Hiperativa/etiologia , Adulto Jovem
15.
BMC Cancer ; 19(1): 453, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092242

RESUMO

BACKGROUND: Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC. METHODS: The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5'-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models. RESULTS: Both genotypes, TC (OR = 0.51, 95% CI = 0.27-0.98) and TT (OR = 0.42, 95% CI = 0.20-0.91) in the locus - 509 of the TGF-ß promoter were significantly associated with GC. The TT genotype in the locus - 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17-0.81). No significant association was found with SNPs IL-4 -590 T/C (rs1800629), IL-6 -573G/C (rs1800796), IL-10 -592C/A (rs1800872), IL-10 -1082A/G (rs1800896), and, IFN-γ -1615C/T (rs2069705). CONCLUSIONS: SNPs in TGFß (- 509 C/T, rs1800469) and IL-10 (- 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.


Assuntos
Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Fator de Crescimento Transformador beta/genética , Adulto , Estudos Transversais , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Neoplasias Gástricas/patologia , Adulto Jovem
16.
PLoS Negl Trop Dis ; 13(5): e0007436, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31120872

RESUMO

Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-ß and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W. bancrofti-infected individuals as well as individuals who were previously infected with W. bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19+CD24highCD38dhigh Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19+CD24highCD5+CD1dhigh and CD19+CD5+CD1dhighIL-10+ Breg as well as CD4+CD127-FOXP3+ Treg frequencies were significantly increased in both W. bancrofti-infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W. bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.


Assuntos
Anti-Helmínticos/administração & dosagem , Linfócitos B Reguladores/imunologia , Filariose Linfática/tratamento farmacológico , Filariose Linfática/imunologia , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Wuchereria bancrofti/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Animais , Filariose Linfática/genética , Filariose Linfática/parasitologia , Feminino , Gana , Humanos , Interleucina-10/genética , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Células Th2/imunologia , Adulto Jovem
17.
Microb Pathog ; 133: 103552, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121269

RESUMO

Aeromonas veronii is an opportunistic pathogen that is capable of infecting both aquatic livestock and mammals. Natural infection in fishes results in irreparable damage to the aquaculture industry. In this study, we sought to investigate whether recombinant Lactobacillus casei expressing the outer membrane protein W (OmpW) of A.veronii could elicit protective immunity against A.veronii infections. We generated two recombinant Lactobacillus casei (L.casei) strains expressing the OmpW of A.veronii (surface-displayed or secreted) and evaluated the effect on immune responses in a fish model. A 600-bp gene fragment was subcloned into the L.casei expression plasmids pPG-1 (surface-displayed) and pPG-2 (secreted). Expression of the recombinant OmpW protein was also confirmed by Western blot and immunofluorescence assays. Common carp immunized with Lc-pPG-1- OmpW and Lc-pPG-2- OmpW via oral administration elicited high serum specific antibody titers and high LZM, ACP, and SOD activities. High levels of the IL-10, IL-ß, IFN-γ, and TNF-α genes in different organs indicated that the inflammatory response and cell immune response were triggered. Additionally, when immunized fish were challenged with A.veronii, Lc-pPG1-OmpW and Lc-pPG2-OmpW demonstrated 40% and 50% protective efficacy. These data indicate that the combination of OmpW delivery and the lactic acid bacteria (LAB) approach may be a promising mucosal therapeutic strategy for treatment of A.veronii.


Assuntos
Aeromonas veronii/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Carpas/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Imunização/veterinária , Lactobacillus casei/metabolismo , Administração Oral , Aeromonas veronii/imunologia , Animais , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/administração & dosagem , Proteínas da Membrana Bacteriana Externa/genética , Vacinas Bacterianas , Sequência de Bases , Carpas/microbiologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Doenças dos Peixes/imunologia , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos/genética , Infecções por Bactérias Gram-Negativas/imunologia , Imunidade Celular , Imunidade Humoral , Interferon gama/genética , Interleucina-10/genética , Intestinos/microbiologia , Lactobacillus casei/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Fator de Necrose Tumoral alfa/genética
18.
Microb Pathog ; 133: 103544, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121270

RESUMO

Interleukin-10 (IL-10) is an anti-inflammatory cytokine associated with the inhibition of HIV replication. IL-10 polymorphisms were found to be linked to drug-induced hepatotoxicity. Hence we examined the prevalence of IL-10 (-819C/T,-1082A/G) polymorphisms in a total of 165 HIV patients which included 34 patients with hepatotoxicity, 131 without hepatotoxicity and 155 healthy controls by the PCR-RFLP method. In HIV patients with hepatotoxicity, the IL-10-819TT genotype increased the risk of ARV associated hepatotoxicity severity (OR = 1.61, P = 0.35). IL-10-819TT genotype was overrepresented in patients with hepatotoxicity as compared to healthy controls (26.5% vs. 13.5%, OR = 1.61, P = 0.46). IL-10 -819CT genotype was associated with advance HIV disease stage (OR = 0.49, P = 0.045). In HIV patients without hepatotoxicity, the IL-10-819TT genotype was more prevalent in patients consuming tobacco as compared to non-users (OR = 1.60, P = 0.41). In HIV patients without hepatotoxicity using both alcohol + efavirenz along with IL-10 -819CT genotype resulted in increased risk for the acquisition of ARV associated hepatotoxicity (OR = 4.00, P = 0.36). In multivariate logistic regression, taking nevirapine was associated with the risk hepatotoxicity severity (OR = 0.23, P = 0.005). In conclusion, an insignificant association between IL-10 polymorphisms and susceptibility to ARV associated hepatotoxicity.


Assuntos
Antirretrovirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Predisposição Genética para Doença , Infecções por HIV/complicações , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas , Benzoxazinas/uso terapêutico , Estudos de Casos e Controles , Citocinas , Suscetibilidade a Doenças , Epistasia Genética , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Análise de Regressão , Fatores de Risco , Índice de Gravidade de Doença , Uso de Tabaco
19.
Infect Immun ; 87(7)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036600

RESUMO

Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in this PTS and measured bacterial growth and PTS gene expression in minimal medium supplemented with selected carbohydrates. We show that E. faecalis upregulates OG1RF_12399 transcription specifically in the presence of gluconate and that E. faecalis strains lacking, or harboring a single point mutation in, OG1RF_12399-12402 are unable to grow in minimal medium containing gluconate. We colonized germfree wild-type and colitis-prone interleukin-10-deficient mice with defined bacterial consortia containing the E. faecalis strains and measured inflammation and bacterial abundance in the colon. We infected macrophage and intestinal epithelial cell lines with the E. faecalis strains and measured intracellular bacterial survival and proinflammatory cytokine secretion. The presence of OG1RF_12399-12402 is not required for E. faecalis colonization of the mouse intestine but is associated with an accelerated onset of experimental colitis in interleukin-10-deficient mice, altered bacterial composition in the colon, enhanced E. faecalis survival within macrophages, and increased proinflammatory cytokine secretion by colon tissue and macrophages. Further studies of bacterial carbohydrate metabolism in general, and E. faecalis PTS-gluconate in particular, during inflammation may identify new mechanisms of disease pathogenesis.


Assuntos
Proteínas de Bactérias/metabolismo , Colite/microbiologia , Enterococcus faecalis/enzimologia , Macrófagos/imunologia , Fosfotransferases/metabolismo , Animais , Proteínas de Bactérias/genética , Colite/genética , Colite/imunologia , Enterococcus faecalis/genética , Enterococcus faecalis/crescimento & desenvolvimento , Feminino , Gluconatos/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Macrófagos/microbiologia , Masculino , Camundongos , Óperon , Fosfotransferases/genética
20.
PLoS Negl Trop Dis ; 13(5): e0007375, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050676

RESUMO

BACKGROUND: The Mayaro virus (MAYV) is an endemic arbovirus in South American countries, where it is responsible for sporadic outbreaks of Mayaro fever. Clinical manifestations include fever, headache, ocular pain, rash, myalgia, and debilitating and persistent polyarthralgia. Understanding the mechanisms associated with MAYV-induced arthritis is of great importance due to the potential for its emergence, urbanization and dispersion to other regions. METHODS: 15-day old Balb/c mice were infected by two distinct pathways, below the forelimb and in the rear footpad. Animals were observed for a period of 21 days. During this time, they were monitored every 24 hours for disease signs, such as weight loss and muscle weakness. Histological damage in the muscles and joints was evaluated 3, 7, 10, 15 and 20 days post-infection. The cytokine profile in serum and muscles during MAYV infection was evaluated by flow cytometry at different post-infection times. For pain analysis, the animals were submitted to the von Frey test and titre in different organs was evaluated throughout the study to obtain viral kinetics. FINDINGS: Infection by two distinct pathways, below the forelimb and in the rear footpad, resulted in a homogeneous viral spread and the development of acute disease in animals. Clinical signs were observed such as ruffled fur, hunched posture, eye irritation and slight gait alteration. In the physical test, both groups presented loss of resistance, which was associated with histopathological damage, including myositis, arthritis, tenosynovitis and periostitis. The immune response was characterized by a strong inflammatory response mediated by the cytokines TNF-α, IL-6 and INF-γ and chemokine MCP-1, followed by the action of IL-10 and IL-4 cytokines. INTERPRETATION: The results showed that Balb/c mice represent a promising model to study mechanisms involved in MAYV pathogenesis and for future antiviral testing.


Assuntos
Infecções por Arbovirus/virologia , Arbovirus/fisiologia , Artrite/virologia , Modelos Animais de Doenças , Miosite/virologia , Animais , Arbovirus/genética , Arbovirus/isolamento & purificação , Feminino , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
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