Endothelial Response to Glucocorticoids in Inflammatory Diseases

Abstract

The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients.

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

“…(close to 100,000 miles long) containing ∼2.5 × 10 12 endothelial cells that are typically flat and susceptible to injury, with a thin basement membrane enriched in type IV collagen and laminin (140). The endothelial lining is in continuous contact with circulating cells and soluble proteins, and the capillaries, represent the primary barrier between elements in the blood and the parenchymal cells.…”

“…The endothelial response to GCs in inflammatory diseases was extensively reviewed covering topics such as inhibition of proinflammatory transcription factors, restoration of endothelial barrier integrity, and induction of protective molecules (140). In experimental sepsis, low-dose glucocorticoid (hydrocortisone or dexamethasone) preserved the endothelial glycocalyx, sustained the vascular barrier and reduced interstitial edema (165,166), and had beneficial effects on mesenteric blood flow and helped with resolution of organ injury (167).…”

The Efficacy and Safety of Glucocorticoids Plus Conventional Therapy for Hepatitis B-Related Liver Failure in China: A Meta-Analysis

“…Antiinflammatory actions of glucocorticoids could be beneficial to stop progressive liver deterioration (10). In addition, their capability of preventing from cytolysis of infected hepatocytes (11), and regulating the plasma levels of TNF, IL-6, CXCL8 (IL-8), and CCL2 (MCP-1) may also play a vital role (38). Importantly, this positive trend could impute the clinical use of blood products, antibiotics, proton pump inhibitors, and nucleoside (acid) analogues in the treatment of liver failure.…”

Dimensional Reconstitution Of The Integral Atherosclerotic Plaque As Integral Atherogenesis.

“…It is important to consider the vaso-regulatory functionalities of groups of endothelial cells as formal agonists in the induction of the atherogenesis as a progressive series of transforming events of the vascular wall. Endothelial cells play a crucial role in inflammation and glucocorticoids affect expression of endothelial cell adhesion molecules, production of pro inflammatory cytokines and chemokines, and maintained integrity of the endothelial barrier (8) . Vaso-regulation relates to dynamics of vasoconstriction and vasodilation as induced particularly by nitric oxide and angiotensin II.…”