TY - JOUR
T1 - Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal cells
AU - Umikawa, Masato
AU - Umikawa, Asako
AU - Asato, Tsuyoshi
AU - Takei, Kimiko
AU - Matsuzaki, Goro
AU - Kariya, Ken Ichi
AU - Zhang, Chengcheng
N1 - Funding Information:
We thank G. Takaesu, N. Mori for technical help. M.U was supported by Astellas Foundation for Research on Metabolic Disorders , Friends of Leukemia Research Fund , Takeda Science Foundation , and JSPS KAKENHI Grant 25460595 . C.C.Z. was supported by NIH grant 1R01CA172268 and Leukemia & Lymphoma Society Award LLS#1024-14 .
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/11/13
Y1 - 2015/11/13
N2 - Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. The purpose of the present study was to elucidate the role of Angptl2 in inflammation by understanding the effects of Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces a drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. Concordantly, proinflammatory cytokines IL-1β, IL-6, TNFα, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and macrophages. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages.
AB - Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. The purpose of the present study was to elucidate the role of Angptl2 in inflammation by understanding the effects of Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces a drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. Concordantly, proinflammatory cytokines IL-1β, IL-6, TNFα, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and macrophages. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages.
KW - Cytokine production
KW - Inflammation
KW - Macrophage
KW - Monocyte
KW - Peritoneal cells
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U2 - 10.1016/j.bbrc.2015.09.183
DO - 10.1016/j.bbrc.2015.09.183
M3 - Article
C2 - 26435501
AN - SCOPUS:84944400960
SN - 0006-291X
VL - 467
SP - 235
EP - 241
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -