@article{a09d8862f1764d518f8405ee906e1ffa,
title = "Interleukin-18 amplifies macrophage polarization and morphological alteration, leading to excessive angiogenesis",
abstract = "M2 macrophage (Mψ) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 Mψs in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse Mψ-like cell line, RAW264.7 cells, and mouse endothelial cell line, b. End5 cells. We discovered that IL-18 acts synergistically with IL-10 to amplify the production of Mψ-derived mediators like osteopontin (OPN) and thrombin, yielding thrombin-cleaved form of OPN generation, which acts through integrins α4/α9, thereby augmenting M2 polarization of Mψ with characteristics of increasing surface CD163 expression in association with morphological alteration. Furthermore, the results of visualizing temporal behavior and morphological alteration of Mψs during angiogenesis demonstrated that M2-like Mψs induced excessive angiogenesis through the direct cell-cell interaction with endothelial cells, possibly mediated by CD163.",
keywords = "Angiogenesis, CD163, Interleukin-18, Macrophage, Osteopontin, Thrombin",
author = "Takuro Kobori and Shinichi Hamasaki and Atsuhiro Kitaura and Yui Yamazaki and Takashi Nishinaka and Atsuko Niwa and Shinichi Nakao and Hidenori Wake and Shuji Mori and Tadashi Yoshino and Masahiro Nishibori and Hideo Takahashi",
note = "Funding Information: The authors would like to thank the staffat the Central Research Facilities, Kindai University Faculty of Medicine, Center for Instrumental Analyses and Center for Morphological Analyses for their technical assistance and are particularly appreciative of Yoshitaka Horiuchi who is a specialist for preparing SEM samples. The authors also would like to thank Editage (www.editage.jp) for English language editing. This work was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (Grant Numbers 15K08253 to HT, 17K01881 to AN), JSPS Grant-in-Aid for Young Scientists (Grant Numbers 15K18996 to TK, 17K16766 to AK), and Japan Agency for Medical Research and Development (AMED) Grant Number 15LK0201014h003 to MN. Additional funding was received from Kindai University Grant-in-Aid for Encouragement of Young Scientists (Grant Number SR16) to TK. HT is also partially supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities (S1411037). Publisher Copyright: {\textcopyright} 2018 Kobori, Hamasaki, Kitaura, Yamazaki, Nishinaka, Niwa, Nakao, Wake, Mori, Yoshino, Nishibori and Takahashi.",
year = "2018",
month = mar,
day = "6",
doi = "10.3389/fimmu.2018.00334",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "MAR",
}