PMID- 25267883 OWN - NLM STAT- MEDLINE DCOM- 20151117 LR - 20150220 IS - 1460-2377 (Electronic) IS - 0953-8178 (Linking) VI - 27 IP - 3 DP - 2015 Mar TI - IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration. PG - 131-41 LID - 10.1093/intimm/dxu090 [doi] AB - 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-4Ralpha, 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-4Ralpha 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. CI - (c) The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Makita, Naoyuki AU - Makita N AD - Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Hizukuri, Yoshiyuki AU - Hizukuri Y AD - Faculty of Exploratory Technology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Yamashiro, Kyoko AU - Yamashiro K AD - Faculty of Exploratory Technology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Murakawa, Masao AU - Murakawa M AD - Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Hayashi, Yasuhiro AU - Hayashi Y AD - 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. LA - eng PT - Journal Article DEP - 20140929 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Antibodies, Blocking) RN - 0 (Chemokine CCL4) RN - 0 (Il4ra protein, mouse) RN - 0 (Receptors, Cell Surface) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Antibodies, Blocking/pharmacology MH - Cell Differentiation MH - Cell Movement/drug effects MH - Cells, Cultured MH - Chemokine CCL4/genetics/*metabolism MH - Eosinophils/*immunology MH - Interleukin-10/immunology/*metabolism MH - Interleukin-4/immunology/*metabolism MH - Macrophage Colony-Stimulating Factor/immunology MH - Macrophages/*immunology/transplantation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Microarray Analysis MH - Phenotype MH - Receptors, Cell Surface/genetics/metabolism MH - Up-Regulation OTO - NOTNLM OT - CCL24 OT - IL-10 OT - IL-4 OT - M2a macrophage OT - eosinophil infiltration EDAT- 2014/10/01 06:00 MHDA- 2015/11/18 06:00 CRDT- 2014/10/01 06:00 PHST- 2014/10/01 06:00 [entrez] PHST- 2014/10/01 06:00 [pubmed] PHST- 2015/11/18 06:00 [medline] AID - dxu090 [pii] AID - 10.1093/intimm/dxu090 [doi] PST - ppublish SO - Int Immunol. 2015 Mar;27(3):131-41. doi: 10.1093/intimm/dxu090. Epub 2014 Sep 29.