TY - JOUR T1 - IL-17 enhances IL-8 production by attenuating both the ARE-mediated and the microRNA-mediated degradation of IL-8 mRNA JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p767 AU - Saheli Chowdhury AU - Annemiek Dijkhuis AU - Rene Lutter Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p767.abstract N2 - Background: Interleukin (IL)-17 is a cytokine implicated in chronic inflammation. Enhanced amounts of IL-17 have been found in the airways of patients with asthma and COPD. Previously we have reported that IL-17 potentiates TNF-α or IL-1β-induced IL-8 and IL-6 production in human lung epithelial cells, predominantly by stabilizing IL-6 and IL-8 mRNA.Aim: IL-6 and IL-8 mRNA contain AU-rich elements (ARE) in the 3'UTR, targeting these mRNAs for facilitated degradation. This decay pathway may be mediated by AU-binding proteins (AU-bps) and possibly microRNAs (miRs). We have assessed whether AUBps (TTP, KHSRP, AUF1) and/or miRs are involved in IL-8 mRNA degradation. And, if so, whether IL-17 modulates these pathways.Results: Inhibition of miR16, or knock-down of TTP or KHSRP resulted in a marked increase of TNF-α-induced IL-8 production, which was paralleled by stabilizing IL-8 mRNA. Conversely, knock-down of AUF-1 reduced IL-8 production and promoted degradation of IL-8 mRNA. IL-17 halts IL-8 mRNA degradation by enhancing the role of AUF1 which protects IL-8 mRNA from degradation. Furthermore, IL-17 reverses the TNF-α-induced production of miR16.Discussion: These findings strongly indicate that IL-17 enhances IL-8 production by attenuating two pathways that degrade IL-8 mRNA. We have obtained similar data for several other inflammatory mediators. Since airway epithelial cells from patients with asthma display enhanced IL-8 production we are assessing whether there is an intrinsic disturbance in these mRNA decay pathways.This work is supported by the Netherlands Asthma Foundation (3.2.06.031) ER -