title: IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration.
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.
authors.affiliation: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Makita
authors.affiliation: Faculty of Exploratory Technology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hizukuri
authors.affiliation: Faculty of Exploratory Technology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamashiro
authors.affiliation: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Murakawa
authors.affiliation: Faculty of Exploratory Technology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan hayashi.yasuhiro.ej@asubio.co.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D019138:Antibodies, Blocking; D054407:Chemokine CCL4; D016753:Interleukin-10; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
keywords: CCL24; IL-10; IL-4; M2a macrophage; eosinophil infiltration