1. IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration
- Author
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Yoshiyuki Hizukuri, Naoyuki Makita, Kyoko Yamashiro, Yasuhiro Hayashi, and Masao Murakawa
- Subjects
Immunology ,Macrophage-activating factor ,Receptors, Cell Surface ,Mice ,Peritoneal cavity ,Eosinophil migration ,Cell Movement ,medicine ,Animals ,Immunology and Allergy ,Antibodies, Blocking ,Chemokine CCL4 ,Cells, Cultured ,Interleukin 4 ,Mice, Inbred BALB C ,biology ,Chemistry ,Macrophage Colony-Stimulating Factor ,Macrophages ,Cell Differentiation ,General Medicine ,Eosinophil ,Microarray Analysis ,Molecular biology ,Interleukin-10 ,Up-Regulation ,Eosinophils ,Mice, Inbred C57BL ,Interleukin 10 ,Phenotype ,medicine.anatomical_structure ,Major basic protein ,biology.protein ,Interleukin-4 ,CCL24 - Abstract
M2 macrophages have been subdivided into subtypes such as IL-4-induced M2a and IL-10-induced M2c in vitro. Although it was reported that IL-10 stimulation leads to an increase in IL-4Rα, the effect of IL-4 and IL-10 in combination with macrophage subtype differentiation remains unclear. Thus, we sought to clarify whether IL-10 enhanced the M2 phenotype induced by IL-4. In this study, we showed that IL-10 enhanced IL-4Rα expression in M-CSF-induced bone marrow-derived macrophages (BMDMs). Global gene expression analysis of M2 macrophages induced by IL-4, IL-10 or IL-4 + IL-10 showed that IL-10 enhanced gene expression of M2a markers induced by IL-4 in M-CSF-induced BMDMs. Moreover, IL-4 and IL-10 synergistically induced CCL24 (Eotaxin-2) production. Enhanced CCL24 expression was also observed in GM-CSF-induced BMDMs and zymosan-elicited, thioglycolate-elicited and naive peritoneal macrophages. CCL24 is a CCR3 agonist and an eosinophil chemoattractant. In vitro, IL-4 + IL-10-stimulated macrophages produced a large amount of CCL24 and increased eosinophil migration, which was inhibited by anti-CCL24 antibody. We also showed that IL-4 + IL-10-stimulated (but not IL-4 or IL-10 alone) macrophages transferred into the peritoneum of C57BL/6J mice increased eosinophil infiltration into the peritoneal cavity. These results demonstrate that IL-4 + IL-10-simulated macrophages have enhanced M2a macrophage-related gene expression, CCL24 production and eosinophil infiltration-inducing activity, thereby suggesting their contribution to eosinophil-related diseases.
- Published
- 2014