Human Endothelium as a Source of Multifunctional Cytokines: Molecular Regulation and Possible Role in Human Disease

Abstract

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.

G-CSF Therapy of Ongoing Experimental Allergic Encephalomyelitis Via Chemokine- and Cytokine-Based Immune Deviation

“…This property may be related to the potent promotion of chemokine synthesis by this cytokine, often exerted in synergy with IFN-␥, on both endothelial cells (30,31) as well as astrocytes (42). Whether this reduction of TNF-␣ levels is a primitive anti-inflammatory effect of G-CSF, as reported in experimental models of endotoxemia (1), or is secondary to the anti-Th1 and pro-Th2 properties also displayed by this molecule (3, 5, 6) remains to be investigated.…”

“…TNF-␣ activates endothelial cells (30,31) and facilitates T cell migration to the CNS. We observed that production of TNF-␣ was 2-fold reduced in macrophages isolated from spleens of G-CSFtreated animals and activated with anti-CD40 to mimic the T cell cognate interaction (Fig.…”

Endothelial cell functions

“…Endothelial cells have the potential to synthesize interleukines, colony-stimulating factors and chemokines (Bierhaus et al, 2000). Upon stimulation by LPS, tumor necrosis factor-a (TNF-a) or IL-1, endothelial cells respond with production and release of these cytokines and growth factors (Pober, 1987;Mantovani et al, 1992;Krishnaswamy et al, 1999). Because endothelial cells also respond to some of the cytokines and growth factors secreted, paracrine, and autocrine stimuli further promote the proinflammatory endothelial response.…”

Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production.

“…Endothelial cells are known to play an important role in regulating vessel permeability and maintaining hemostasis. 5 Certain pathogens can infect endothelial cells and alter functions such as cytokine production, adhesion molecule expression, permeability, and procoagulation activity, [6][7][8][9] resulting in a deregulation of hemostasis. Therefore, in this study, we examined whether DV could infect HUVEC and the cytokine production by HUVEC in response to the infection.…”