RESUMO
Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)-10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was designed to investigate a possible association between alleles carried at position -1082 in the promoter region of the IL-10 gene and clinical data on 378 patients with CF. After adjustment for potential confounding variables, a significant relationship was found between the -1082GG genotype and both colonization with Aspergillus fumigatus and allergic bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were observed in patients colonized with A. fumigatus. These results suggest that polymorphisms in the promoter region of the IL-10 gene may influence the host response to A. fumigatus in the context of CF.
Assuntos
Aspergilose/imunologia , Aspergillus fumigatus , Fibrose Cística/imunologia , Interleucina-10/genética , Pneumopatias Fúngicas/imunologia , Polimorfismo Genético/imunologia , Adolescente , Criança , Pré-Escolar , Fibrose Cística/genética , Fibrose Cística/microbiologia , HumanosRESUMO
OBJECTIVES: Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF. METHODS: Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9. RESULTS: No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children. CONCLUSIONS: These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF.
Assuntos
Fibrose Cística/genética , Glutationa Transferase/genética , Isoenzimas/genética , Adolescente , Adulto , Sequência de Bases , Criança , Estudos de Coortes , Fibrose Cística/fisiopatologia , Primers do DNA , Humanos , Pessoa de Meia-IdadeRESUMO
The NaCl content of airway surface fluid is believed to be of central importance in lung pathology. To test whether the Na+ concentration could influence the inflammatory response in human bronchial epithelial cells (BECs), we investigated the interleukin (IL)-8 and RANTES expression in BECs exposed to an isotonic sea-water derived low Na+ (ISW) saline compared to isotonic 0.9% NaCl saline. Exposure of BECs to ISW saline caused a significant decrease in IL-8 and RANTES gene expression and protein production as compared to that observed with 0.9% NaCl saline. Furthermore, we observed a concomitant reduction of phosphorylated IkappaBalpha associated with a marked inhibition of NF-kappaB-DNA binding activity in BECs exposed to ISW saline as compared to 0.9% NaCl saline. These findings support a new role for Na+ in the pathogenesis of airway inflammatory disorders. Therapies targeted at lowering Na+ level in airway epithelium may be beneficial in treating inflammatory lung diseases.
