Increased IL-6 Trans-Signaling in the Airways After an Allergen Challenge

The pro-inflammatory cytokine IL-6 is elevated in both blood and airways in asthma. IL-6 signaling is regulated by its receptor composed of two proteins, IL-6R and GP130, that are found in both membrane and soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signaling in cells such as epithelial cells and fibroblasts, which express GP130, but do not produce sufficient IL-6R. We aimed to analyze IL-6 trans-signaling in the airways after an allergen challenge and to examine the potential source of sIL-6R and sGP130. In addition to protein analysis of bronchoalveolar lavages by ELISA and flow cytometry, we performed next-generation RNA sequencing (RNA-seq) to study the expression of the IL-6R subunits by eosinophils activated by IL-3 in vitro. RNA-seq and proteomic analyses confirmed that eosinophils do not produce GP130 but produce both IL-6R and ADAM10, a metalloproteinase that cleaves membrane IL-6R into sIL-6R. Overall design: Gene expression profiles of blood eosinophils from three subjects with allergy and mild asthma that were cultured in RPMI and 10% serum with or without IL-3 (2 ng/ml) for 4 h and 20 h.