Contrasting effects of stanniocalcin-related polypeptides on macrophage foam cell formation and vascular smooth muscle cell migration

Yamamoto, Keigo; Tajima, Yukie; Hasegawa, Akinori; Takahashi, Yasuhiro; Kojima, Miho; Watanabe, Ryoji; Sato, Kengo; Shichiri, Masayoshi; Watanabe, Takuya

doi:10.1016/j.peptides.2016.06.009

Cited by 11 publications

(12 citation statements)

References 38 publications

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“…The interaction between HRG and STC2 was further validated by coimmunoprecipitation. In VitD 3 -treated U937 cells, STC2 negatively regulated CD14 þ cell differentiation, in line with the described ability of peptides derived from STC1 and STC2 to directly affect inflammatory cell function (44). Crucially, transcript analyses in U937 cells treated with HRG or STC2 individually or in combination indicated that HRG modulated certain immunoregulatory changes seen in STC2-treated cells.…”

Section: Discussionsupporting

confidence: 68%

Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity

Roche

Pietilä

Kaito

et al. 2018

Molecular Cancer Therapeutics

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The plasma-protein histidine-rich glycoprotein (HRG) is implicated in phenotypic switching of tumor-associated macrophages, regulating cytokine production and phagocytotic activity, thereby promoting vessel normalization and antitumor immune responses. To assess the therapeutic effect of HRG gene delivery on CNS tumors, we used adenovirus-encoded HRG to treat mouse intracranial GL261 glioma. Delivery of Ad5-HRG to the tumor site resulted in a significant reduction in glioma growth, associated with increased vessel perfusion and increased CD45 leukocyte and CD8 T-cell accumulation in the tumor. Antibody-mediated neutralization of colony-stimulating factor-1 suppressed the effects of HRG on CD45 and CD8 infiltration. Using a novel protein interaction-decoding technology, TRICEPS-based ligand receptor capture (LRC), we identified Stanniocalcin-2 (STC2) as an interacting partner of HRG on the surface of inflammatory cells and colocalization of HRG and STC2 in gliomas. HRG reduced the suppressive effects of STC2 on monocyte CD14 differentiation and STC2-regulated immune response pathways. In consequence, Ad5-HRG-treated gliomas displayed decreased numbers of IL35 Treg cells, providing a mechanistic rationale for the reduction in GL261 growth in response to Ad5-HRG delivery. We conclude that HRG suppresses glioma growth by modulating tumor inflammation through monocyte infiltration and differentiation. Moreover, HRG acts to balance the regulatory effects of its partner, STC2, on inflammation and innate and/or acquired immunity. HRG gene delivery therefore offers a potential therapeutic strategy to control antitumor immunity. .

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Section: Discussionsupporting

confidence: 68%

Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity

Roche

Pietilä

Kaito

et al. 2018

Molecular Cancer Therapeutics

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“…We have investigated the atheroprotective properties of a large number of novel human endogenous peptides, such as salusin-α, heregulin-β1, omentin-1, catestatin-1, urocortin-1, stanniocalcin-1, and incretins (glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide) [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Now we are paying more attention to tumor necrosis factor-stimulated gene-6 (TSG-6) as an anti-atherogenic protein [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Watanabe

Sato

Ozawa

et al. 2018

IJMS

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Tumor necrosis factor-stimulated gene-6 (TSG-6) is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC) migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability) and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD), plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

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“…Monocytes were purified using anti‐CD14 antibody‐conjugated magnetic microbeads. Monocytes were subsequently seeded into 3.5‐cm dishes (1×10 6 cells/1 mL per dish) for cholesterol esterification assays and immunoblots . Cells were incubated at 37°C in a 5% CO 2 humidified incubator for 7 days in RPMI‐1640 medium supplemented with 10% human serum, 0.05 mg/mL streptomycin, 50 U/mL penicillin, and the indicated concentrations of neopterin.…”

Section: Methodsmentioning

confidence: 99%

“…HMDMs were differentiated by 7‐day culture with human serum and the indicated concentrations of neopterin, with incubation for another 19 hours at 37°C in 5% CO 2 with the same concentrations of neopterin, together with 50 μg/mL oxLDL in the presence of 100 μmol/L [ 3 H]oleate conjugated with BSA . Cellular lipids were extracted, and the radioactivity attributed to cholesterol‐[ 3 H]oleate was determined by thin‐layer chromatography.…”

Section: Methodsmentioning

confidence: 99%

Neopterin Counters Vascular Inflammation and Atherosclerosis

Shirai

Sato

Yamashita

et al. 2018

JAHA

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BackgroundNeopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed.Methods and ResultsWe investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte‐derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E–deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF‐α (tumor necrosis factor α)–induced upregulation of MCP‐1 (monocyte chemotactic protein 1), ICAM‐1 (intercellular adhesion molecule 1), and VCAM‐1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF‐α–induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF‐κB (nuclear factor‐κB) downregulation. Neopterin suppressed oxidized low‐density lipoprotein–induced foam cell formation associated with CD36 downregulation and upregulation of ATP‐binding cassette transporters A1 and G1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II–induced migration and proliferation via c‐Src/Raf‐1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E–deficient mice.ConclusionsOur results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.

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Contrasting effects of stanniocalcin-related polypeptides on macrophage foam cell formation and vascular smooth muscle cell migration

Cited by 11 publications

References 38 publications

Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity

Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Neopterin Counters Vascular Inflammation and Atherosclerosis

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