Enhanced production of vascular endothelial growth factor by human monocytic cells stimulated with endotoxin through transcription factor SP-1

Sakuta, Tetsuya; Matsushita, Kazunobu; Yamaguchi, Noboru; Oyama, Tohru; Motani, Rie; Kinoshita, Toshihiko; Nagaoka, Sumiharu; Abeyama, Kazuhiro; Maruyama, Ikuro; Takada, Haruhiko; Torii, Mitsuo

doi:10.1099/0022-1317-50-3-233

Cited by 33 publications

(26 citation statements)

References 11 publications

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“…Similar to the observations for cytokine secretion shown in Fig. 1B, and consistent with literature observations (33,34), TNF-a gene expression was significantly reduced to basal levels (p , 0.001) during endotoxin tolerance (4 h after the second treatment) (Fig. 3A), as was tissue factor (p , 0.01).…”

Section: Microarray Analysis Revealed Strong Differences In Gene Exprsupporting

confidence: 80%

“…Additionally, endotoxin tolerance led to the overrepresentation of dysregulated genes with binding sites for the transcription factors important in woundhealing processes. For example, the TFBS for Sp1, a transcription factor involved in angiogenesis through AKT-mediated induction of VEGF expression, was overrepresented (33,45). The TFBS for members of the ETS family like ETS-1, ELF-1, and SPI1 which are involved in regulation of extracellular matrix (46), vascular development (47), and cellular migration (48), were also significantly overrepresented during endotoxin tolerance.…”

Section: Discussionmentioning

confidence: 97%

“…Gene expression analysis by qRT-PCR showed that growth factors VEGF and FGF-2 ( Fig. 5B), previously described to be produced by human monocytes (33,38), were significantly induced during tolerance conditions (p , 0.01 and p , 0.05, respectively). Similar results were observed for the metalloproteinases MMP-7 and MMP-9 (p , 0.05).…”

Section: Microarray Analysis Revealed Strong Differences In Gene Exprmentioning

confidence: 99%

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Endotoxin Tolerance Represents a Distinctive State of Alternative Polarization (M2) in Human Mononuclear Cells

Pena

Pistolic

Raj

et al. 2011

The Journal of Immunology

216

212

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Classical (M1) and alternative (M2) polarization of mononuclear cells (MNCs) such as monocyte and macrophages is known to occur in response to challenges within a microenvironment, like the encounter of a pathogen. LPS, also known as endotoxin, is a potent inducer of inflammation and M1 polarization. LPS can also generate an effect in MNCs known as endotoxin tolerance, defined as the reduced capacity of a cell to respond to LPS activation after an initial exposure to this stimulus. Using systems biology approaches in PBMCs, monocytes, and monocyte-derived macrophages involving microarrays and advanced bioinformatic analysis, we determined that gene responses during endotoxin tolerance were similar to those found during M2 polarization, featuring gene and protein expression critical for the development of key M2 MNC functions, including reduced production of proinflammatory mediators, expression of genes involved in phagocytosis, as well as tissue remodeling. Moreover, expression of different metallothionein gene isoforms, known for their role in the control of oxidative stress and in immunomodulation, were also found to be consistently upregulated during endotoxin tolerance. These results demonstrate that after an initial inflammatory stimulus, human MNCs undergo an M2 polarization probably to control hyperinflammation and heal the affected tissue.

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Section: Microarray Analysis Revealed Strong Differences In Gene Exprsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 97%

Section: Microarray Analysis Revealed Strong Differences In Gene Exprmentioning

confidence: 99%

See 1 more Smart Citation

Endotoxin Tolerance Represents a Distinctive State of Alternative Polarization (M2) in Human Mononuclear Cells

Pena

Pistolic

Raj

et al. 2011

The Journal of Immunology

216

212

View full text Add to dashboard Cite

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“…The Sp1 element is regulated independently of HIF1 by a large number of factors, including fluid shear stress (Urbich et al 2003), oxidative stress (Sen et al 2002;Schafer et al 2003), interferon ␣ (von Marschall et al 2003, retinoic acid (Maeno et al 2002), HPV16 E6 (Lopez-Ocejo et al 2000, p73 (Salimath et al 2000), p53 (Zhang et al 2000;Pal et al 2001), endotoxin (Sakuta et al 2001), VHL (Mukhopadhyay et al 1997), and PDGF (Finkenzeller et al 1997). The mechanisms of regulation are far from being resolved, but they include protein-protein interactions and stability (Mukhopadhyay et al 1997), increased binding due to phosphorylation (Milanini-Mongiat et al 2002;Reisinger et al 2003), and increased synthesis (Maeno et al 2002).…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Net regulates the angiogenic switch

Zheng¹,

Wasylyk²,

Ayadi³

et al. 2003

Genes Dev.

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Angiogenesis is fundamental to physiological and pathological processes. Despite intensive efforts, little is known about the intracellular circuits that regulate angiogenesis. The transcription factor Net is activated by phosphorylation induced by Ras, an indirect regulator of angiogenesis. Net is expressed at sites of vasculogenesis and angiogenesis during early mouse development, suggesting that it could have a role in blood vessel formation. We show here that down-regulation of Net inhibits angiogenesis and vascular endothelial growth factor (VEGF) expression in vivo, ex vivo, and in vitro. Ras-activated phosphorylated Net (P-Net) stimulates the mouse VEGF promoter through the −80 to −53 region that principally binds Sp1. P-Net and VEGF are coexpressed in angiogenic processes in wild-type mouse tissues and in human tumors. We conclude that Net is a regulator of angiogenesis that can switch to an activator following induction by pro-angiogenic molecules.

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“…1). Полученные нами результаты совпадают с описанными ранее в литературе данными о возможности индуциро-ванной секреции указанных молекул клетками линии ТHP-1 и моноцитами периферической крови в присутствии различных активаторов [11,13,19,20,24,25,27].…”

Section: результатыunclassified

Effects of Secretable Placental Factors Upon Secretion of Cytokines by THP-1 Monocyte-Like Cells

Онохина¹,

Львова²,

Tsitskarava³

et al. 2014

Med.Imm.Rus

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Влияние фактороВ, секретируемых тканью плаценты, на секрецию цитокиноВ моноцитоподобной линией клеток тнр-1 Онохина Я.С., Львова Т.Ю., Цицкарава Д.З., Сельков С.А., Соколов Д.И. ФГБУ «Научно-исследовательский институт акушерства и гинекoлогии им. Д.О. Отта» СЗО РАМН, Санкт-Петербург, РоссияРезюме. Находясь в маточно-плацентарном кровотоке, моноциты подвергаются действию факто-ров, секретируемых тканью плаценты, которые влияют на их функциональное состояние при бере-менности. В настоящем исследовании на модели in vitro проведено сравнительное изучение влияния растворимых продуктов ткани плацент, полученных от женщин с физиологической и осложненной гестозом беременностью, на секрецию цитокинов моноцитоподобными клетками линии ТНР-1. Установлено, что секреция VEGF клетками линии ТНР-1 была выше, а секреция IL-6, IL-8 и MCP-1 была ниже в присутствии растворимых факторов ткани плацент третьего триместра беременности по сравнению с первым триместром беременности. Секреция IL-6 и MCP-1 клетками линии ТНР-1 была выше, а секреция растворимой формы рецептора TNFRII была ниже в присутствии раствори-мых факторов ткани плацент женщин с гестозом по сравнению с физиологической беременностью.Работа выполнена при финансовой поддержке Министерства образования и науки РФ ГК № 02.740.11.0711 и грантов Президента РФ № НШ-3594.2010.7 и МД-150.2011.7. Оригинальные статьиOriginal articles Медицинская иммунология 2013, Т. 15, № 3, стр. 227-234 © 2013, СПб РО РААКИ Medical Immunology 2013, Vol. 15, 3, pp. 227-234 © 2013 Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells) was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.

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Enhanced production of vascular endothelial growth factor by human monocytic cells stimulated with endotoxin through transcription factor SP-1

Cited by 33 publications

References 11 publications

Endotoxin Tolerance Represents a Distinctive State of Alternative Polarization (M2) in Human Mononuclear Cells

Endotoxin Tolerance Represents a Distinctive State of Alternative Polarization (M2) in Human Mononuclear Cells

The transcription factor Net regulates the angiogenic switch

Effects of Secretable Placental Factors Upon Secretion of Cytokines by THP-1 Monocyte-Like Cells

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