| First Author | Heller NM | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 6 | Pages | e39673 |
| PubMed ID | 22761864 | Mgi Jnum | J:187918 |
| Mgi Id | MGI:5438736 | Doi | 10.1371/journal.pone.0039673 |
| Citation | Heller NM, et al. (2012) IL-4 engagement of the type I IL-4 receptor complex enhances mouse eosinophil migration to eotaxin-1 in vitro. PLoS One 7(6):e39673 |
| abstractText | BACKGROUND: Previous work from our laboratory demonstrated that IL-4Ralpha expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function. METHODS: Standard Transwell chemotaxis assay was used to assay migration of mouse eosinophils and signal transduction was assessed by Western blotting. RESULTS: Here we determined that (i) mouse eosinophils express both type I and type II IL-4 receptors, (ii) in contrast to human eosinophils, mouse eosinophils do not chemotax to IL-4 or IL-13 although (iii) pre-treatment with IL-4 but not IL-13 enhanced migration to eotaxin-1. This IL-4-mediated enhancement was dependent on type I IL-4 receptor expression: gammaC-deficient eosinophils did not show enhancement of migratory capacity when pre-treated with IL-4. In addition, mouse eosinophils responded to IL-4 with the robust tyrosine phosphorylation of STAT6 and IRS-2, while IL-13-induced responses were considerably weaker. CONCLUSIONS: The presence of IL-4 in combination with eotaxin-1 in the allergic inflammatory milieu could potentiate infiltration of eosinophils into the lungs. Therapies that block IL-4 and chemokine receptors on eosinophils might be more effective clinically in reducing eosinophilic lung inflammation. |
