RESUMO
AIMS: To assess the importance of tumour necrosis factor alpha (TNF-alpha) promoter polymorphism in relation to infection with the cytotoxin associated gene A (cagA) subtype of Helicobacter pylori within a dyspeptic Korean population. METHODS: Eighty three patients with gastric disease and 113 healthy controls were studied. The DNA from gastric biopsy specimens was analysed by H pylori specific and cagA specific polymerase chain reaction (PCR). To characterise TNF-alpha polymorphism at positions -308 and -238, PCR based restriction fragment length polymorphism analysis was performed. RESULTS: Helicobacter pylori infection was closely correlated with G to A transition at position -308 of the TNF-alpha promoter when compared with healthy controls (odds ratio (OR), 2.912; 95% confidence interval (CI), 1.082 to 7.836; p = 0.034). Although TNF-alpha -308 polymorphism in patients with H pylori was not significantly different from that in patients without H pylori, the -308A polymorphism was strongly associated with H pylori cagA subtype infection when compared with the polymorphism in cagA negative H pylori infection (OR, 8.757; 95% CI, 1.413 to 54.262; p = 0.019) and healthy controls (OR, 3.683; 95% CI, 1.343 to 10.101; p = 0.011). G to A genetic change at position -238 of the TNF-alpha gene was not significantly associated with H pylori cagA subtype infection. In addition, genetic polymorphisms at both sites of the TNF-alpha promoter in patients with H pylori infection did not correlate with the severity of disease. CONCLUSION: TNF-alpha -308A polymorphism was significantly related to infection with the H pylori cagA subtype in Korean patients with gastric disease.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Polimorfismo Genético , Gastropatias/genética , Fator de Necrose Tumoral alfa/genética , Técnicas de Tipagem Bacteriana , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Gastropatias/microbiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologiaRESUMO
Here we report that lymphocyte functions were down-regulated by cyanobacterial hepatotoxin microcystin. Treatment of three microcystin (MC) isotypes, MC-LR, MC-YR and nodularin, on B6C3F1 mouse splenocytes produced dose-dependent inhibition of in vitro polyclonal antibody response and lymphoproliferation to LPS. ConA-induced lymphoproliferative response was decreased by MC-YR and nodularin, but no significant effect was observed in the MC-LR treatment. Intraperitoneal administration of nodularin into B6C3F1 mice decreased humoral immune responses to sheep red blood cell (sRBC), and the inhibitory effect became severe when hepatic uptake of nodularin was blocked by rifampicin. Each MC 1 microM suppressed phorbol 12-myristate 13-acetate (PMA) plus ionomycin-induced IL-2 mRNA expression in splenocytes and thymocytes, but not in EL-4 mouse thymoma cells. To further characterize the mechanism for the reduced IL-2 mRNA level, IL-2 mRNA stability was measured using RT-PCR. Deprivation of PMA/ionomycin stimuli from activated splenocytes and blockade of new transcription resulted in destabilization of IL-2 mRNA, which was accelerated by MC treatment. These results demonstrated that MC down-regulated lymphocyte functions and the immunosuppression was mediated, at least in part, through decreased IL-2 mRNA stability.
Assuntos
Interleucina-2/genética , Peptídeos Cíclicos/farmacologia , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Toxinas Bacterianas/química , Toxinas Bacterianas/farmacologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Microcistinas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linfócitos T/citologia , Linfócitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais CultivadasRESUMO
We investigated the potential association of tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms with cancers. The study included 169 patients with gastric cancer, uterine cervical cancer, colorectal cancer, or renal cell carcinoma and 92 healthy controls. The -308 and -238 polymorphisms in the TNF-alpha promoter were analyzed by PCR-restriction fragment length polymorphism (RFLP). The proportion of individuals carrying the TNF-238A allele was significantly lower in the cancer group than in the control group. The odds ratio for cancer in subjects with the TNF-238A allele was 0.25 (95% CI, 0.10-0.64). No association was found between the -308 polymorphism and cancers. These results suggest that the -238A allele has a protective function against cancers.