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A3873 - The Impact of Wnt Signaling-Modulated IL-17A-Mediated Macrophage Polarization on Epithelial-Mesenchymal Transition in Murine Airway Epithelial Cells
Author Block: C. Yuan1, G. Bai2, K. Bao2, M. Luo2, X. Liu2; 1College of Life Science, Ningxia University, Yinchuan,Ningxia, Yinchuan, China, 2Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resou, College of Life Science, Ningxia University, Yinchuan,Ningxia, Yinchuan, China.
Macrophages are professional immune cells that paly key roles in maintaining the immune homeostasis. The polarization of macrophages may vary according to the distribution and microenvironment of resided tissues, and exposed stimuli. In this regard, two major subtypes of polarized macrophages are characterized, i.e. classic activated macrophages (M1) and alternative activated macrophages (M2). The inflammation has been suggested as an initial cause of pulmonary fibrosis, and the induction of epithelial-mesenchymal transition (EMT) in epithelail cells promotes the pathogenesis of pulmonary fibrosis. Wnt signals are key cellular signaling in maintaining tissue homeostatsis and injury repair, which also play important roles in immune regulation. The IL-17 signaling is an immune modulator able to shape macrophage phenotypes, and is related to host defense and a variety of immune-related diseases. A compelling body of studies revealed that both Wnt signaling and IL-17 were abberrently expressed in pulmonary fibrosis. The aim of this study was therefore to interrogate impacts of Wnt signaling-altered IL-17A-mediated macrophage polarization on mesenchymal properties in murine airway epithelial cells. To this end, a co-culture of RAW264.7 macrophages and primary mouse tracheal epithelial cells that were fully differentiated in an air-liquid interface (ALI) state was employed. The effects of Wnt signals on IL-17-induced macrophage polarization was ascertained by immunoblotting assay and cytometric analysis for macrophage markers, and the impact of Wnt signaling-regulated IL-17-altered macrophages on EMT in murine epithelial cells were accessed by determined the expression of TGF-β signaling and EMT markers. The results showed that the canonical Wnt signaling ligand Wnt3a altered IL-17-induced macrophage M1 to M2 phenotype, while the non-canonical Wnt ligand Wnt5a could enhance the IL-17-induced macrophage M1 function and inhibit the M2 activity, suggesting an interaction between canonical and non-canonical Wnt signaling in the balance of IL-17-activatied inflammations. Functionally, an activation of canonical Wnt/β-catenin signaling and non-canonical Wnt signaling led a significant attenuation and eleviation of IL-17A-induced inflammation in RAW264.7 cells, respectively. Currently, studies in the impact of cellular communications between ALI epithelial cells and IL-17-shaped macrophages on mesenchymal properties of epithelial cells, and the consequence and mechanism of the Wnt signal-modulated IL-17-activated macrophages in EMT of epithelial cells are undergoing. We suspect that an inbalance of Wnt signaling activity in interactions between pulmonary epithelial cells and macrophages may be of importance in the EMT and pathogenesis of pulmonary fibrosis. The study thus will provide an insight into the mechanism of immune regulation in pulmonary fibrosis.