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.
| Original language | English |
|---|---|
| Article number | 334 |
| Journal | Frontiers in Immunology |
| Volume | 9 |
| Issue number | MAR |
| DOIs | |
| Publication status | Published - Mar 6 2018 |
Fingerprint
Keywords
- Angiogenesis
- CD163
- Interleukin-18
- Macrophage
- Osteopontin
- Thrombin
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Interleukin-18 amplifies macrophage polarization and morphological alteration, leading to excessive angiogenesis. / Kobori, Takuro; Hamasaki, Shinichi; Kitaura, Atsuhiro; Yamazaki, Yui; Nishinaka, Takashi; Niwa, Atsuko; Nakao, Shinichi; Wake, Hidenori; Mori, Shuji; Yoshino, Tadashi; Nishibori, Masahiro; Takahashi, Hideo.
In: Frontiers in Immunology, Vol. 9, No. MAR, 334, 06.03.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-18 amplifies macrophage polarization and morphological alteration, leading to excessive angiogenesis
AU - Kobori, Takuro
AU - Hamasaki, Shinichi
AU - Kitaura, Atsuhiro
AU - Yamazaki, Yui
AU - Nishinaka, Takashi
AU - Niwa, Atsuko
AU - Nakao, Shinichi
AU - Wake, Hidenori
AU - Mori, Shuji
AU - Yoshino, Tadashi
AU - Nishibori, Masahiro
AU - Takahashi, Hideo
PY - 2018/3/6
Y1 - 2018/3/6
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - CD163
KW - Interleukin-18
KW - Macrophage
KW - Osteopontin
KW - Thrombin
UR - http://www.scopus.com/inward/record.url?scp=85042907383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042907383&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.00334
DO - 10.3389/fimmu.2018.00334
M3 - Article
AN - SCOPUS:85042907383
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - MAR
M1 - 334
ER -