Microarray analysis of poly(I:C) and IL-13 co-stimulated human airway epithelium

Abstract

In asthma patients, viral infections can trigger exacerbations characterized by an acute worsening of the disease with the loss of symptom control, systemic corticosteroid medication or even hospitalization. This study aimed at examining the epithelial response early during an asthma exacerbation using an in vitro model of primary human bronchial epithelial cells (HBEs). HBEs were cultured at air-liquid interface (ALI)-conditions. Asthma features were induced by treatment with human interleukin-13 (IL-13). Stimulation with poly(I:C) was used to mimic a virus triggering exacerbation in vitro. Gene expression profiling was performed by microarray analysis. Viruses are recognized e.g. by the receptors RIG-1 and MDA-5. These proteins are encoded by DDX58 (DExD/H-box helicase 58) and IFIH1 (interferon induced with helicase C domain 1) which are highly expressed in co-stimulated cultures compared to poly(I:C) or IL-13 alone. The inflammation is highly increased by a significantly exaggerated expression of pro-inflammatory mediators such as IL-6 and TNF-α (tumour necrosis factor alpha) after IL-13 and poly(I:C) treatment. Furthermore, the antiviral response via interferon signalling is induced. Interferon (IFN)-β1 is significantly increased in co-stimulated cultures compared to poly(I:C) alone and the IFN induced proteins IFIT1, IFIT3 and ISG15 are expressed at their highest levels. We suggest that this in vitro ALI cell culture model is suitable to mimic asthma exacerbations at the level of airway epithelium. Analysis of expression profiles will help deciphering epithelial mechanisms in the very early phase of an asthma exacerbation.