CD40 expression and function in human dermal endothelial cells is regulated by 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.

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Surgical procedures suppress autophagic flux in the kidney

Cell Death and Disease ◽

10.1038/s41419-021-03518-w ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Carolyn N. Brown ◽

Daniel Atwood ◽

Deepak Pokhrel ◽

Sara J. Holditch ◽

Christopher Altmann ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Mammalian Target Of Rapamycin ◽

Kidney Injury ◽

Compensatory Hypertrophy ◽

Autophagic Flux ◽

Bafilomycin A1 ◽

Concomitant Increase ◽

Sham Surgery ◽

And Function ◽

Pro Inflammatory Cytokines

AbstractMany surgical models are used to study kidney and other diseases in mice, yet the effects of the surgical procedure itself on the kidney and other tissues have not been elucidated. In the present study, we found that both sham surgery and unilateral nephrectomy (UNX), which is used as a model of renal compensatory hypertrophy, in mice resulted in increased mammalian target of rapamycin complex 1/2 (mTORC1/2) in the remaining kidney. mTORC1 is known to regulate lysosomal biogenesis and autophagy. Genes associated with lysosomal biogenesis and function were decreased in sham surgery and UNX kidneys. In both sham surgery and UNX, there was suppressed autophagic flux in the kidney as indicated by the lack of an increase in LC3-II or autophagosomes seen on immunoblot, IF and EM after bafilomycin A1 administration and a concomitant increase in p62, a marker of autophagic cargo. There was a massive increase in pro-inflammatory cytokines, which are known to activate ERK1/2, in the serum after sham surgery and UNX. There was a large increase in ERK1/2 in sham surgery and UNX kidneys, which was blocked by the MEK1/2 inhibitor, trametinib. Trametinib also resulted in a significant decrease in p62. In summary, there was an intense systemic inflammatory response, an ERK-mediated increase in p62 and suppressed autophagic flux in the kidney after sham surgery and UNX. It is important that researchers are aware that changes in systemic pro-inflammatory cytokines, ERK1/2 and autophagy can be caused by sham surgery as well as the kidney injury/disease itself.

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Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

Journal of Rheumatic Diseases ◽

10.4078/jrd.2016.23.3.148 ◽

2016 ◽

Vol 23 (3) ◽

pp. 148 ◽

Cited By ~ 3

Author(s):

Semun Seong ◽

Jung Ha Kim ◽

Nacksung Kim

Keyword(s):

Inflammatory Cytokines ◽

Osteoclast Differentiation ◽

And Function ◽

Pro Inflammatory Cytokines

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CD40 expression and function on human dermal microvascular endothelial cells: role in cutaneous inflammation

Clinical and Experimental Dermatology ◽

10.1046/j.1365-2230.2001.00853.x ◽

2001 ◽

Vol 26 (5) ◽

pp. 434-440 ◽

Cited By ~ 10

Author(s):

S. R. Singh ◽

K. Casper ◽

S. Summers ◽

R. A. Swerlick

Keyword(s):

Endothelial Cells ◽

Microvascular Endothelial Cells ◽

Cutaneous Inflammation ◽

Cd40 Expression ◽

Microvascular Endothelial ◽

And Function

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OP0106 The Impact of Pro-Inflammatory Cytokines on the Expression and Function of Long Noncoding RNA (LNCRNA) in Rheumatoid Arthritis Synovial Fibroblasts

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-eular.3308 ◽

2014 ◽

Vol 73 (Suppl 2) ◽

pp. 101.1-101

Author(s):

M. Frank Bertoncelj ◽

M. Trenkmann ◽

C. Kolling ◽

B.A. Michel ◽

R.E. Gay ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Cytokines ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Synovial Fibroblasts ◽

And Function ◽

The Impact ◽

Pro Inflammatory Cytokines

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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

10.1101/2020.05.08.083618 ◽

2020 ◽

Cited By ~ 3

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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