Anti-Inflammatory Mechanisms in the Vascular Wall

Abstract

Abstract-The role of vascular cells during inflammation is critical and is of particular importance in inflammatorydiseases, including atherosclerosis, ischemia/reperfusion, and septic shock. Research in vascular biology has progressed remarkably in the last decade, resulting in a better understanding of the vascular cell responses to inflammatory stimuli. Most of the vascular inflammatory responses are mediated through the IB/nuclear factor-B system. Much recent work shows that vascular inflammation can be limited by anti-inflammatory counteregulatory mechanisms that maintain the integrity and homeostasis of the vascular wall. The anti-inflammatory mechanisms in the vascular wall involve anti-inflammatory external signals and intracellular mediators. The anti-inflammatory external signals include the anti-inflammatory cytokines, transforming growth factor-␤, interleukin-10 and interleukin-1 receptor antagonist, HDL, as well as some angiogenic and growth factors. Physiological laminar shear stress is of particular importance in protecting endothelial cells against inflammatory activation. Its effects are partly mediated through NO production. Finally, endogenous cytoprotective genes or nuclear receptors, such as the peroxisome proliferator-activated receptors, can be expressed by vascular cells in response to proinflammatory stimuli to limit the inflammatory process and the injury. nflammation is a basic pathological mechanism that underlies a variety of diseases. The inflammatory reaction involves the complex interactions between inflammatory cells (neutrophils, lymphocytes, and monocytes/macrophages) and vascular cells (endothelial cells [ECs] and smooth muscle cells [SMCs]). The role of vascular cells during the inflammatory process is critical. Multiple cytokines and growth factors are present at sites of inflammation, and each of these can potentially influence the nature of the inflammatory response. ECs and SMCs must integrate the signals generated by these multiple factors to effectively regulate the immunoinflammatory response through the expression of adhesion molecules, cytokines, chemokines, matrix metalloproteinases, and growth factors. Research in vascular biology has progressed remarkably in the last decade, resulting in a better understanding of the vascular cell responses to inflammatory stimuli and resulting in the identification of major intracellular inflammatory signaling pathways, particularly the IB/nuclear factor-B (NF-B) system. Much recent work shows that vascular inflammation can be limited by anti-inflammatory counteregulatory mechanisms that maintain the integrity and homeostasis of the vascular wall. This might be of particular importance in inflammatory diseases, such as atherosclerosis, septic shock, or ischemia/reperfusion. The purpose of the present review is to describe recent advances in the understanding of the anti-inflammatory mechanisms in vascular cells, focusing on anti-inflammatory external signals and intracellular mediators Original

Deficient expression of interleukin‐10 receptor α chain in rheumatoid arthritis synovium: Limitation of animal models of inflammation

“…Normal mesenchymal lining cells (11) and OA synovial fibroblasts express IL-10R␣. In RA synovium, we observed that the expression of IL-10R␣ (if any) was mainly restricted to the perivascular region, in spite of the fact that a previous study (12) demonstrated that normal vascular tissue does not show IL-10R␣. Already this difference reflects a pathologic alteration and could also explain the lack of quantitative difference in IL-10R␣ mRNA using whole synovial tissues (i.e., neoangiogenesis being an important pathophysiologic process in RA).…”

Interleukin-35 Inhibits Endothelial Cell Activation by Suppressing MAPK-AP-1 Pathway

“…Most anti-inflammatory mechanisms in the vascular wall, including IL-10, TGF-␤, high density lipoprotein, and peroxisome proliferator-activated receptor ␣ activators, are mediated by inhibition of the NF-B pathway (31). IL-10 decreases leukocyte vein extravasation through inhibition of endothelial expression of P-selectin, E-selectin, and ICAM-1 (32).…”

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

“…Regional differences in cytokine-induced release and responsiveness to mediators appear to contribute to the dilator or constrictor responses observed in a specific vascular bed (42). Vascular cells may also respond to antiinflammatory counterregulatory mechanisms, including antiinflammatory cytokines, which maintain vascular wall integrity and homeostasis (40,42). IL-10, one of the main anti-inflammatory cytokines, displays vasculoprotective properties (42), and we can speculate that IL-10 is playing an important role, i.e., preventing ET-1-induced vascular injuries.…”