Pro-inflammatory activity and oxidative stress on a line of Cystic Fibrosis (CF) human respiratory epithelium

JUAN M. FIGUEROA; MARÍA MACARENA MASSIP COPIZ; DORIS PRIMROSE; MARIÁNGELES CLAUZURE; CONSUELO MORI; TOMÁS A. SANTA COLOMA; ANGEL GABRIEL VALDIVIESO; ANDREA V. DUGOUR

Paris

Congreso; European Respiratory Society (ERS) International Congress 2018; 2018

European Respiratory Society (ERS)

Introduction: Inflammation and oxidative stress are central in CF lung damage. IL-1ß produced by respiratory epithelium, appears to be key in this.Objective: To study the regulation of the IL-1ß 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-1ß, anti-IL-1ß, IL-1 receptor antagonist and CFTR inhibitor. Cells were incubated at different Cl concentrations in presence of ionophores. Protein expression, secretion of IL-1ß 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-1ß than control cell line. Inhibition of CFTR in control cells increased IL-1ß. Intracellular Cl- concentrations are higher in CF cells and CFTR inhibited cells. High intracellular Cl elevated IL-1ß mRNA and protein expression. Treatments IL-1ß receptor antagonist andanti-IL-1ß receptor inhibited these changes. CF cells showed a reduction of 50% in mCx-I and an increase in ROS. IL-1ß in cells re-established CFTR reduced mCx-I and increased ROS. Incubation IL-1ß or anti-IL-1ß 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 < 0.05).Discussion/Conclusion: The CFTR dysfunction leads to an increase in intracellular Cl that promotes maturation and release of IL-1ß. The autocrine action of IL-1ß on cells receptor of IL-1ß induces mitochondrial dysfunctin and oxidative stress, and increases synthesis of IL-1ß mRNA resulting in a proinflammatory loop.