Interleukin-1 Beta Enhances IL-8 Release From A549 Cell Through The Activation Of ERK1/2, P38 Mitogen-activated Protein Kinase

Objective: The release of inflammatory mediators from mechanical ventilation is one mechanism of ventilator associated lung injury (VALI) and referred to as biotrauma. The intracellular signalling molecules that are activated by ventilation are the same as those utilized by inflammatory cytokines. We investigated the effect of IL-1βon IL-8 release from A549 cell and underlying signal transduction pathways. Methods :Activation of extracellular signal regulated kinases-1/2 (ERK-1/2) and p38 mitogen-activated protein kinase (p38) was determined by Western blot with specific antibody. RT-PCR and ELISA were used to quantify IL-8 mRNA and protein expression respectively. Results: IL-1βinduced rapid phosphorylation of ERK1/2 and p38 . IL-1βsignificantly augmented IL-8 mRNA expression and secretion. U0126, a specific inhibitor for MEK1/2, abolished phosphorylation of ERK1/2, 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 SB203580. Conclusions: These results suggest that IL-1βinduces IL-8 mRNA expression and protein release in A549 cells through activation of ERK1/2 and in part of p38 MAPK. Our data suggests the specific MAPKs inhibitors could be useful treatments to minimize the biotrauma.