Regulated Expression of the IL-31 Receptor in Bronchial and Alveolar Epithelial Cells,Pulmonary Fibroblasts,and Pulmonary Macrophages

Abstract

Interleukin-31 (IL-31), an IL-6 cytokine family member, is proposed to play a role in animal models of airway hyperreactivity. It is produced by activated T cells and signals via a heterodimeric receptor complex composed of IL-31Rα and OSMRβ. Only low levels of IL-31Rα expression have been demonstrated in pulmonary epithelial cell lines, however, and little is known about the ability to regulate its expression and signaling. Therefore, primary cultures of human bronchial and alveolar epithelial cells, pulmonary fibroblasts, pulmonary macrophages, and established lines of immortalized bronchial epithelial cells (HBE) and alveolar carcinoma cells (A549) were analyzed by RT-PCR, immunoblotting, and thymidine incorporation. Distinct, cell type-specific regulation of IL-31Rα expression was detected. Transforming growth factor-β (TGF-β) enhanced IL-31Rα mRNA expression in primary cultures and established lines of epithelial cells, but not in macrophages. In contrast, interferon-γ (IFN-γ) induced IL-31Rα mRNA expression in macrophages. IL-31Rα protein expression was below detection threshold in primary epithelial cell cultures but was detectable in A549 cells and increased with TGF-β treatment. In HBE and A549 cells, TGF-β pretreatment increased IL-31-mediated Stat3 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. In A549 cells, TGF-β magnified IL-31-dependent suppression of proliferation. The data suggest that increased IL-31Rα expression correlates with an enhanced response to IL-31.