GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-α converting enzyme (TACE)

被引：99

作者：

Hiasa, Masahiro ^{[1
,2
,3
]}

Abe, Masahiro ^{[1
]}

Nakano, Ayako ^{[1
]}

Oda, Asuka ^{[1
]}

Amou, Hiroe ^{[1
]}

Kido, Shinsuke ^{[1
]}

Takeuchi, Kyoko ^{[1
]}

Kagawa, Kumiko ^{[1
]}

Yata, Kenichiro ^{[1
]}

Hashimoto, Toshihiro ^{[1
]}

Ozaki, Shuji ^{[1
]}

Asaoka, Kenzo ^{[2
]}

Tanaka, Eiji ^{[3
]}

Moriyama, Keiji ^{[4
]}

Matsumoto, Toshio ^{[1
]}

机构：

[1] Univ Tokushima, Grad Sch Med, Dept Med & Bioregulatory Sci, Tokushima 7708503, Japan

[2] Univ Tokushima, Grad Sch Oral Sci, Dept Biomat & Bioengn, Tokushima 7708503, Japan

[3] Univ Tokushima, Grad Sch Oral Sci, Dept Orthodont & Dentofacial Orthoped, Tokushima 7708503, Japan

[4] Tokyo Med & Dent Univ, Dept Maxillofacial Orthognath, Tokyo, Japan

来源：

BLOOD | 2009年 / 114卷 / 20期

关键词：

COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; BONE-MARROW MACROPHAGES; MULTIPLE-MYELOMA; MONOCYTE DIFFERENTIATION; PROTEIN-KINASE; INTERLEUKIN-4; PROGENITORS; GROWTH; METALLOPROTEINASES;

D O I：

10.1182/blood-2009-04-215020

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Monocytes give rise to macrophages, osteoclasts (OCs), and dendritic cells (DCs). Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB (RANK) ligand induce OC differentiation from monocytes, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) trigger monocytic differentiation into DCs. However, regulatory mechanisms for the polarization of monocytic differentiation are still unclear. The present study was undertaken to clarify the mechanism of triggering the deflection of OC and DC differentiation from monocytes. GM-CSF and IL-4 abolished monocytic differentiation into OCs while inducing DC differentiation even in the presence of M-CSF and RANK ligand. GM-CSF and IL-4 in combination potently up-regulate tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) and activity in monocytes, causing ectodomain shedding of M-CSF receptor, resulting in the disruption of its phosphorylation by M-CSF as well as the induction of osteoclastogenesis from monocytes by M-CSF and RANK ligand. Interestingly, TACE inhibition robustly causes the resumption of the surface expression of M-CSF receptor on monocytes, facilitating M-CSF-mediated phosphorylation of M-CSF receptor and macrophage/OC differentiation while impairing GM-CSF- and IL-4-mediated DC differentiation from monocytes. These results reveal a novel proteolytic regulation of M-CSF receptor expression in monocytes to control MCSF signaling and monocytic differentiation into macrophage/OC-lineage cells or DCs. (Blood. 2009;114:4517-4526)

引用

页码：4517 / 4526

页数：10

共 52 条

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