Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages

2010 ◽  
Vol 62 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Sara Costa ◽  
Francesca Zimetti ◽  
Matteo Pedrelli ◽  
Giovanni Cremonesi ◽  
Franco Bernini
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Human Endothelial Cells ◽  
Cytokines Secretion ◽  
Pro Inflammatory Cytokines

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals Synthesis of 1,25-Dihydroxyvitamin D3 by Human Endothelial Cells Is Regulated by Inflammatory Cytokines: A Novel Autocrine Determinant of Vascular Cell Adhesion

2002 ◽  
Vol 13 (3) ◽  
pp. 621-629
Author(s):  
Daniel Zehnder ◽  
Rosemary Bland ◽  
Ravinder S. Chana ◽  
David C. Wheeler ◽  
Alexander J. Howie ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Inflammatory Cytokines ◽  
Vascular Tissue ◽  
Umbilical Vein ◽  
Primary Cultures ◽  
Human Endothelial Cells ◽  
Functional Studies ◽  
Reverse Transcription Pcr ◽  
Umbilical Vein Endothelial Cells

ABSTRACT. In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent nonclassical effects. In particular, local production of 1,25D3 catalyzed by the enzyme 1α-hydroxylase (1α-OHase) may act as an autocrine/paracrine immunomodulatory mechanism. To investigate the significance of this in vascular tissue the expression and function of 1α-OHase in human endothelial cells was characterized. Immunohistochemical and in situ hybridization analyses show, for the first time, the presence of 1α-OHase mRNA and protein in endothelial cells from human renal arteries as well as postcapillary venules from lymphoid tissue. Reverse transcription–PCR and Western blot analyses confirmed the presence of 1α-OHase in primary cultures of human umbilical vein endothelial cells (HUVEC). Enzyme activity in HUVEC (318 ± 56 fmoles 1,25(OH)2D3/hr/mg protein) increased after treatment with tumor necrosis factor–α (1054 ± 166, P < 0.01), lipopolysaccharide (1381 ± 88, P < 0.01), or forskolin (554 ± 56, P < 0.05). Functional studies showed that exogenously added 1,25(OH)2D3 or its precursor, 25-hydroxyvitamin D3 (25(OH)D3), significantly decreased HUVEC proliferation after 72 h of treatment (33% and 11%, respectively). In addition, after 24 h treatment, both 1,25(OH)2D3 and 25(OH)D3 increased the adhesion of monocytic U937 cells to HUVEC (159% and 153%, respectively). These data indicate that human endothelia are able to produce active vitamin D. The rapid induction of endothelial 1α-OHase activity by inflammatory cytokines suggests a novel autocrine/paracrine role for the enzyme, possibly as a modulator of endothelial cell adhesion.

scholarly journals NQO1 Alleviates Renal Fibrosis by Inhibiting TLR4/NF-κB and TGF-β/Smad Signaling Pathway in Diabetic Nephropathy

2021 ◽  
Author(s):  
Duojun Qiu ◽  
Shan Song ◽  
Yawei Bian ◽  
Chen Yuan ◽  
wei zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Expression ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Renal Tubular ◽  
Tgf Β1 ◽  
Cytokines Secretion ◽  
Pro Inflammatory Cytokines

Abstract Background: Diabetic nephropathy is one of the main complications of diabetes, inflammation and fibrosis play an important role in its progress. NAD (P) H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and toxic quinone damage. In present study, we aimed to investigate the protective effects and underlying mechanisms of NQO1 on diabetes-induced renal inflammation and fibrosis. Methods: In vivo, adeno-associated virus serotype 9 was used to infect the kidneys of type 2 diabetes model db/db mice to overexpress NQO1. In vitro, human renal tubular epithelial cells (HK-2) transfected with NQO1 pcDNA were cultured in high glucose. The gene and protein expression were assessed by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemical staining. Mitochondrial reactive oxygen species was detected by MitoSox red. Result: Our study revealed that the expression of NQO1 was markedly down-regulated, Toll-like receptor 4 (TLR4) and TGF-β1 upregulated in vivo and in vitro under diabetic conditions. Overexpression of NQO1 suppressed pro-inflammatory cytokines secretion (IL-6, TNF-α, MCP-1), extracellular matrix (ECM) accumulation (collagen Ⅳ, Fibronectin) and epithelial-mesenchymal transition (EMT) (α-SMA, E-cadherin) in db/db mice kidney and high glucose cultured human renal tubular cells (HK-2). Furthermore, NQO1 overexpression ameliorated high glucose-induced TLR4/NF-κB and TGF-β/Smad pathway activation. Mechanistic studies demonstrated that TLR4 inhibitor (TAK-242) suppressed TLR4/NF-κB signaling pathway, pro-inflammatory cytokines secretion, EMT and ECM-related protein expression in HG-exposed HK-2 cells. In addition, we found that antioxidants NAC and tempol increased the expression of NQO1, decreased the expression of TLR4, TGF-β1, Nox1, Nox4 and ROS production in HK-2 cells cultured with high glucose. Conclusions: These above data suggest that NQO1 alleviates diabetes-induced renal inflammation and fibrosis by regulating TLR4/NF-κB and TGF-β/Smad signaling pathways.

scholarly journals Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19

2020 ◽  
Author(s):  
Xiaohan Ren ◽  
Xiyi Wei ◽  
Guangyao Li ◽  
Shancheng Ren ◽  
Xinglin Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Urinary Tract ◽  
Inflammatory Cytokines ◽  
Kidney Diseases ◽  
Single Cells ◽  
Expression Patterns ◽  
Clinical Manifestations ◽  
Gene Set Enrichment Analysis ◽  
Human Testis ◽  
Pro Inflammatory Cytokines

AbstractBackgroundSince December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. From previously published evidence, ACE2 and TMPRSS2, are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Meanwhile, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome that is often observed in critically ill patients.MethodsWe investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially under specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2 specific signature.ResultsOur results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis, and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were remarkably concentrated in endothelial cells, macrophages, and spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging mechanisms via autoimmune attacks.ConclusionsThis study provided new insights into the pathogenicity mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.

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