Adipose-derived mesenchymal stem cells modulate CD14++CD16+ expression on monocytes from sepsis patients in vitro via prostaglandin E2

Qiu, Guanguan; Zheng, Guoping; Ge, Menghua; Huang, Lan-Fang; Tong, Haijiang; Chen, Ping; Lai, Dengming; Hu, Yinan; Cheng, Baoli; Shu, Qiang; Xu, Jianguo

doi:10.1186/s13287-017-0546-x

Cited by 26 publications

(25 citation statements)

References 48 publications

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“…Intermediate monocytes are the least characterized of the monocyte subtypes in humans, however, these cells have been implicated in inflammatory diseases such as Kawasaki disease, 45 rheumatoid arthritis, 15 sepsis, 46 HIV, 47 acute heart failure, and coronary artery disease. 48 Using deuterium labelling in humans, Patel et al recently showed a sequential transition of classical monocytes that emerge from the bone marrow to the intermediate and subsequently the non-classical phenotype.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Loperena

Beusecum

Itani

et al. 2018

Cardiovascular Research

129

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AimsMonocytes play an important role in hypertension. Circulating monocytes in humans exist as classical, intermediate, and non-classical forms. Monocyte differentiation can be influenced by the endothelium, which in turn is activated in hypertension by mechanical stretch. We sought to examine the role of increased endothelial stretch and hypertension on monocyte phenotype and function.Methods and resultsHuman monocytes were cultured with confluent human aortic endothelial cells undergoing either 5% or 10% cyclical stretch. We also characterized circulating monocytes in normotensive and hypertensive humans. In addition, we quantified accumulation of activated monocytes and monocyte-derived cells in aortas and kidneys of mice with Angiotensin II-induced hypertension. Increased endothelial stretch enhanced monocyte conversion to CD14++CD16+ intermediate monocytes and monocytes bearing the CD209 marker and markedly stimulated monocyte mRNA expression of interleukin (IL)-6, IL-1β, IL-23, chemokine (C-C motif) ligand 4, and tumour necrosis factor α. STAT3 in monocytes was activated by increased endothelial stretch. Inhibition of STAT3, neutralization of IL-6 and scavenging of hydrogen peroxide prevented formation of intermediate monocytes in response to increased endothelial stretch. We also found evidence that nitric oxide (NO) inhibits formation of intermediate monocytes and STAT3 activation. In vivo studies demonstrated that humans with hypertension have increased intermediate and non-classical monocytes and that intermediate monocytes demonstrate evidence of STAT3 activation. Mice with experimental hypertension exhibit increased aortic and renal infiltration of monocytes, dendritic cells, and macrophages with activated STAT3.ConclusionsThese findings provide insight into how monocytes are activated by the vascular endothelium during hypertension. This is likely in part due to a loss of NO signalling and increased release of IL-6 and hydrogen peroxide by the dysfunctional endothelium and a parallel increase in STAT activation in adjacent monocytes. Interventions to enhance bioavailable NO, reduce IL-6 or hydrogen peroxide production or to inhibit STAT3 may have anti-inflammatory roles in hypertension and related conditions.

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Section: Discussionmentioning

confidence: 99%

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Loperena

Beusecum

Itani

et al. 2018

Cardiovascular Research

129

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“…Western Blot Analysis. Western blot analysis was performed as described previously [21]. Protein samples were extracted from PBMC of control, infection, and sepsis groups at admission.…”

Section: Total Rna Extraction From Peripheral Bloodmentioning

confidence: 99%

miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

Zheng

Qiu

et al. 2020

Mediators of Inflammation

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Background. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition. Methods. A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes. Results. miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-κB pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-α, and MCP-1. Conclusions. PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.

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“…8,9 This macrophage activation was shown to occur via the cyclo-oxygenase (COX)-2/prostaglandin pathway in septic patients. 13 hASCs may therefore help control the inflammatory response at the acute phase of severe sepsis and improve outcome. hASCs are routinely obtained enzymatically from fat lipoaspirate (LA) as stromal vascular fraction (SVF), and, in most cases, undergo further ex vivo expansion.…”

Section: Abstract: Human Adipose Stem Cells; Inflammation; Mesenchymamentioning

confidence: 99%

Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model

Bouglé

Rocheteau

Hivelin

et al. 2018

British Journal of Anaesthesia

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Background: Severe sepsis has a high mortality rate. There is increasing evidence that human mesenchymal stem cells possess immunomodulatory properties in sepsis, particularly those from adipose tissue. We hypothesised that microfragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis. Methods: Micro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 h after caecal ligation and puncture (CLP) in C57Bl/6RJ ketamineexylazine anaesthetised mice. The primary endpoint was the inflammatory score. Secondary endpoints included survival, physiological, histological, and biological parameters. Results: In CLP mice, micro-fragmented fat administration significantly decreased the median (range) inflammatory score compared with saline [17 (14e20) vs 9 (8e12), P¼0.006]. Secondary endpoints were also significantly improved in micro-fragmented fat-treated compared with saline-treated CLP mice. Improvement in inflammatory score and in survival was suppressed when micro-fragmented fat was co-administered with liposomes loaded with clodronate (macrophage toxin) or NS-398 (cyclo-oxygenase 2 inhibitor), but not with SC-560 (cyclo-oxygenase 1 inhibitor).

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Adipose-derived mesenchymal stem cells modulate CD14++CD16+ expression on monocytes from sepsis patients in vitro via prostaglandin E2

Cited by 26 publications

References 48 publications

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model

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