| Autor: |
Consuelo Mori, Mariángeles Clauzure, Ángel Gabriel Valdivieso, Tomás A. Santa Coloma, María M. Massip-Copiz, Juan Manuel Figueroa, Andrea V. Dugour, Doris Primrose |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Cystic fibrosis. |
| DOI: |
10.1183/13993003.congress-2018.pa3423 |
| Popis: |
Introduction: Inflammation and oxidative stress are central in CF lung damage. IL-1s produced by respiratory epithelium, appears to be key in this. Objective: To study the regulation of the IL-1s in cultured CF respiratory epithelium. Materials and Methods: A CF respiratory epithelium and the same line with re-established CFTR gene were cultivated. Both were treated with exogenous IL-1s, anti-IL-1s, IL-1 receptor antagonist and CFTR inhibitor. Cells were incubated at different Cl concentrations in presence of ionophores. Protein expression, secretion of IL-1s was measured. Cellular ROS and mitochondrial complex I (mCx-I) were determinate. Statistical analysis: ANOVA and Tukey tests. Results: CF cells released 40% more IL-1s than control cell line. Inhibition of CFTR in control cells increased IL-1s. Intracellular Cl- concentrations are higher in CF cells and CFTR inhibited cells. High intracellular Cl elevated IL-1s mRNA and protein expression. Treatments IL-1s receptor antagonist and anti-IL-1s receptor inhibited these changes. CF cells showed a reduction of 50% in mCx-I and an increase in ROS. IL-1s in cells re-established CFTR reduced mCx-I and increased ROS. Incubation IL-1s or anti-IL-1s receptor restored mCx-I activity and ROS to normal values in CF cells. (All trials performed in triplicate); and data expressed three independent experiments (p Discussion/Conclusion: The CFTR dysfunction leads to an increase in intracellular Cl that promotes maturation and release of IL-1s. The autocrine action of IL-1s on cells receptor of IL-1s induces mitochondrial dysfunctin and oxidative stress, and increases synthesis of IL-1s mRNA resulting in a pro-inflammatory loop. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
