The Regulation Mechanism Of IL-8 Released By Lung Epithelial Cells

Objective:mechanical ventilation has become one of indispensable supports for critical illness.The release of inflammatory mediators following mechanical ventilation and its subsequent adverse effect to the patient is one of the mechanisms related ventilator associated lung injury(VALI).The intracellular signalling pathways involved in have not been fully investigated. The release patterns of inflammatory cytokines after mechanical ventilation in vitro and vivo have been reported similar as stimulated by specific pro-inflammatory cytokines,such as interleukin 1 beta.The effect of IL-1βon IL-8 release from A549 cell and its possible underlying signal transduction pathways,NF-κB pathway,were investigated in this study.Methods:ELISA and RT-PCR were used to quantify IL-8 protein and mRNA expression respectively.Activation of I-kappa B kinase(IKK),one of NF-κB components,was determined by westem blot with specific antibody. IL-1βsignificantly augmented IL-8 protein release and mRNA expression. IL-1βinduced rapid phosphorylation of I-κB.AS602868,a specific inhibitor for IKK2,abolish the phosphorylation of I-κB,and suppressed the expression of both IL-8 protein and mRNA.Results:IL-1βinduced rapid phosphorylation of I-κB.IL-1βsignificantly augmented IL-8 mRNA expression and secretion.AS602868,a specific inhibitor for IKK2,abolished phosphorylation of I-κB,and suppressed the expression of both IL-8 mRNA and protein.In response to IL-1β,IL-8 protein but not IL-8 mRNA was attenuated by AS602868. Conclusion:these results suggested that IL-1βinduced IL-8 protein secretion and mRNA expression in A549 cells via the activation of NF-κB signaling pathway,indicated that it would be useful to inhibit the activation of NF-κB to minimize the biotrauma.