Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of experimental sepsis

Al-Banna, Nadia; Pavlović, Dragan; Sharawi, Nivin; Bac, Vo Hoai; Jaskulski, Mathis; Balzer, Claudius; Weber, Stefan; Nedeljkov, Vladimir; Lehmann, Christian

doi:10.1016/j.mvr.2014.07.010

Cited by 9 publications

(8 citation statements)

References 27 publications

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“…In humans, DHEA is produced in the adrenal cortex, the gonads, and the CNS (27)(28)(29)(30). In tissues, DHEA displays anti-inflammatory properties, including inhibition of leukocyte recruitment (31,32). DHEA can bind to nuclear receptors, such as estrogen receptor a and b (33,34).…”

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confidence: 99%

DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

Ziogas

Maekawa

Wießner³

et al. 2020

The Journal of Immunology

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Leukocytes are rapidly recruited to sites of inflammation via interactions with the vascular endothelium. The steroid hormone dehydroepiandrosterone (DHEA) exerts anti-inflammatory properties; however, the underlying mechanisms are poorly understood. In this study, we show that an anti-inflammatory mechanism of DHEA involves the regulation of developmental endothelial locus 1 (DEL-1) expression. DEL-1 is a secreted homeostatic factor that inhibits b2-integrin-dependent leukocyte adhesion, and the subsequent leukocyte recruitment and its expression is downregulated upon inflammation. Similarly, DHEA inhibited leukocyte adhesion to the endothelium in venules of the inflamed mouse cremaster muscle. Importantly, in a model of lung inflammation, DHEA limited neutrophil recruitment in a DEL-1-dependent manner. Mechanistically, DHEA counteracted the inhibitory effect of inflammation on DEL-1 expression. Indeed, whereas TNF reduced DEL-1 expression and secretion in endothelial cells by diminishing C/EBPb binding to the DEL-1 gene promoter, DHEA counteracted the inhibitory effect of TNF via activation of tropomyosin receptor kinase A (TRKA) and downstream PI3K/AKT signaling that restored C/EBPb binding to the DEL-1 promoter. In conclusion, DHEA restrains neutrophil recruitment by reversing inflammation-induced downregulation of DEL-1 expression. Therefore, the anti-inflammatory DHEA/DEL-1 axis could be harnessed therapeutically in the context of inflammatory diseases.

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confidence: 99%

DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

Ziogas

Maekawa

Wießner³

et al. 2020

The Journal of Immunology

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“…Microcirculatory changes in the intestine begin early in the course of the disease. A reduction of intestinal blood flow is observed particularly in the mucosal layer and may cause epithelial damage [14]. Bacterial translocation from the gut lumen into the circulation can occur and further activate the systemic immune response, thereby contributing to the severity of multiorgan failure [15].…”

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confidence: 99%

Anti-inflammatory and anti-bacterial effects of iron chelation in experimental sepsis

Islam

Jarosch

Parquet³

et al. 2016

Journal of Surgical Research

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“…FCD refers to the length of the red blood cell-perfused capillaries per unit area, which indicates the quality of capillary perfusion [30, 31]. Rolling leukocytes were defined as white blood cells moving along endothelial cells at velocities lower than the red blood cells in the centerline stream [32]. During leukocyte-endothelial cell interactions, some leukocytes adhere to the blood vessel wall.…”

Section: Methodsmentioning

confidence: 99%

Local Biological Reactions and Pseudotumor-Like Tissue Formation in relation to Metal Wear in a Murine In Vivo Model

Paulus

Ebinger

Cheng

et al. 2019

BioMed Research International

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Metal wear debris and released ions (CoCrMo), which are widely generated in metal-on-metal bearings of hip implants, are also found in patients with metal-on-polyethylene bearings due to the mechanically assisted crevice corrosion of modular taper junctions, including head-neck and neck-stem taper interfaces. The resulting adverse reactions to metal debris and metal ions frequently lead to early arthroplasty revision surgery. National guidelines have since been published where the blood metal ion concentration of patients must consistently be monitored after joint replacement to prevent serious complications from developing after surgery. However, to date, the effect of metal particles and metal ions on local biological reactions is complex and still not understood in detail; the present study sought to elucidate the complex mechanism of metal wear-associated inflammation reactions. The knee joints in 4 groups each consisting of 10 female BALB/c mice received injections with cobalt chrome ions, cobalt chrome particles, and ultra-high-molecular-weight polyethylene (UHMWPE) particles or PBS (control). Seven days after injection, the synovial microcirculation and knee joint diameter were assessed via intravital fluorescence microscopy followed by histological evaluation of the synovial layer. Enlarged knee diameter, enhanced leukocyte to endothelial cell interactions, and an increase in functional capillary density within cobalt chrome particle-treated animals were significantly greater than those in the other treatment groups. Subsequently, pseudotumor-like tissue formations were observed only in the synovial tissue layer of the cobalt chrome particle-treated animals. Therefore, these findings strongly suggest that the cobalt chrome particles and not metal ions are the cause for in vivo postsurgery implantation inflammation.

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Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of experimental sepsis

Cited by 9 publications

References 27 publications

DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

Anti-inflammatory and anti-bacterial effects of iron chelation in experimental sepsis

Local Biological Reactions and Pseudotumor-Like Tissue Formation in relation to Metal Wear in a Murine In Vivo Model

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