Interleukin‐1‐β‐Activated Microvascular Endothelial Cells Promote DC‐SIGN + Alternative Macrophages Associated with Skin Fibrosis in Systemic Sclerosis

2021 ◽  
Author(s):  
Paôline Laurent ◽  
Joelle Lapoirie ◽  
Damien Leleu ◽  
Emeline Levionnois ◽  
Cyrielle Grenier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Interleukin 1 ◽  
Skin Fibrosis ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

scholarly journals Anti-Inflammatory Effect and Cellular Uptake Mechanism of Carbon Nanodots in in Human Microvascular Endothelial Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1247
Author(s):  
Sarah Belperain ◽  
Zi Yae Kang ◽  
Andrew Dunphy ◽  
Brandon Priebe ◽  
Norman H. L. Chiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Synthesis Method ◽  
Microvascular Endothelial Cells ◽  
Carbon Nanodots ◽  
Uptake Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Microvascular Endothelial

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.

scholarly journals Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Tetsuya Ikawa ◽  
Takuya Miyagawa ◽  
Yuki Fukui ◽  
Satoshi Toyama ◽  
Jun Omatsu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Vascular Permeability ◽  
Dermal Fibroblasts ◽  
Microvascular Endothelial Cells ◽  
Clinical Samples ◽  
Mrna Levels ◽  
Angiogenic Activity ◽  
Microvascular Endothelial

Abstract Background We have recently demonstrated that serum CCL20 levels positively correlate with mean pulmonary arterial pressure in patients with systemic sclerosis (SSc). Considering a proangiogenic effect of CCL20 on endothelial cells via CCR6, the CCL20/CCR6 axis may contribute to the development of SSc vasculopathy. Therefore, we explored this hypothesis using clinical samples, cultured cells, and murine SSc models. Methods The expression levels of CCL20 and CCR6 in the skin, mRNA levels of target genes, and the binding of transcription factor FLI1 to the target gene promoter were evaluated by immunostaining, quantitative reverse transcription PCR, and chromatin immunoprecipitation, respectively. Vascular permeability was evaluated by Evans blue dye injection in bleomycin-treated mice. Angiogenic activity of endothelial cells was assessed by in vitro angiogenesis assay. Results CCL20 expression was significantly elevated in dermal fibroblasts of patients with early diffuse cutaneous SSc, while CCR6 was significantly up-regulated in dermal small vessels of SSc patients irrespective of disease subtypes and disease duration. In human dermal microvascular endothelial cells, FLI1 siRNA induced the expression of CCR6, but not CCL20, and FLI1 bound to the CCR6 promoter. Importantly, vascular permeability, a representative SSc-like vascular feature of bleomycin-treated mice, was attenuated by Ccr6 siRNA treatment, and CCR6 siRNA suppressed the angiogenic activity of human dermal microvascular endothelial cells assayed by in vitro tube formation. Conclusions The increased expression of endothelial CCR6 due to FLI1 deficiency may contribute to the development of SSc vasculopathy.

Induction of NO synthase in rat cardiac microvascular endothelial cells by IL-1 beta and IFN-gamma

1995 ◽  
Vol 268 (3) ◽  
pp. H1293-H1303 ◽  
Author(s):  
J. L. Balligand ◽  
D. Ungureanu-Longrois ◽  
W. W. Simmons ◽  
L. Kobzik ◽  
C. J. Lowenstein ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Interleukin 1 ◽  
No Synthase ◽  
Microvascular Endothelial Cells ◽  
Inos Mrna ◽  
Microvascular Endothelium ◽  
Ifn Gamma ◽  
Nitrite Production ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

There are important phenotypic differences between endothelial cells of large vessels and the microvasculature and among microvascular endothelial cells isolated from different tissues and organs. In contrast to most macrovascular endothelial cells, we demonstrate that cultured cardiac microvascular endothelial cells (CMEC) have no detectable constitutive NO synthase (NOS) activity but have a robust increase in NOS activity in response to specific inflammatory cytokines. To determine the identity of the inducible NOS (iNOS) isoform(s) induced by cytokines, we used reverse-transcription polymerase chain reaction techniques to clone and sequence a 217-bp cDNA fragment from CMEC cultures pretreated with interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) that was identical to the corresponding portion of the murine macrophage iNOS cDNA. By use of this CMEC iNOS cDNA as a probe in Northern analyses, IL-1 beta, but not IFN-gamma, increased iNOS mRNA content in CMEC, although IFN-gamma markedly potentiated iNOS induction in these cells. In IL-1 beta- and IFN-gamma-pretreated CMEC, dexamethasone only minimally suppressed the rise in iNOS mRNA, protein abundance, or maximal iNOS enzyme activity in whole cell lysates but suppressed nitrite production by 60% in intact CMEC. Dual labeling of cytokine-pretreated CMEC in primary culture with an anti-iNOS antiserum and a fluorescein-labeled lectin specific for the microvascular endothelium of rat heart (GS-1) confirmed the presence of iNOS expression in these cells. iNOS was also detected in microvascular endothelium in situ in ventricular muscle from lipopolysaccharide-, but not sham-injected, rat hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

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