Interleukin (IL)-6 and IL-10 Induce Decorin mRNA in Endothelial Cells, but Interaction with Fibrillar Collagen Is Essential for Its Translation

Abstract

Decorin, a small multifunctional proteoglycan, is expressed by sprouting endothelial cells (ECs) during inflammation-induced angiogenesis in vivo and by human ECs co-cultured with fibroblasts in a collagen lattice. To investigate how decorin is induced, human EA.hy 926 ECs and/or human umbilical vein ECs were treated with interleukin (IL)-10 and IL-6. Both treatments induced decorin mRNA in human ECs. IL-6 and IL-10 led to a dose-dependent mRNA increase with a maximum at 10 and 50 ng/ml, respectively. The combination of both interleukins together had a stronger effect than one alone. Immunostaining demonstrated that both interleukins caused decorin synthesis in ECs and the formation of capillary-like structures in a collagen lattice. However, immunoprecipitations of interleukin-treated ECs cultured on plastic were negative. Only interleukin-stimulated ECs grown on a collagen type I matrix or growth factor-reduced Matrigel were able to synthesize the proteoglycan. Acid-soluble collagen type I did not support decorin protein synthesis. The addition of antibodies to ␣ 1 or ␣ 2 integrins or the ␣ 2 integrin inhibitor rhodocetin led to an inhibition of synthesis. These data show that IL-10 and IL-6 induce decorin mRNA transcription, but additional signals from the extracellular matrix are necessary for its translation.

Decorin Regulates Endothelial Cell Motility on Collagen I through Activation of Insulin-like Growth Factor I Receptor and Modulation of α2β1 Integrin Activity

“…Since the endothelial cells did not produce endogenous decorin under our noninflammatory culture conditions (Fig. 4C, right, lane 3), in line with previous results (12), the detected decorin must have originated from exogenously added decorin. Only the intact proteoglycan could be detected where decorin had been added to the To analyze Rac activity, serum-starved adherent endothelial cells were stimulated with 0.7 M decorin in serum-free medium for the indicated times, and active Rac was precipitated from cell lysates with p21-activated kinase binding domain beads.…”

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study

“…Among many functions as a pro-inflammatory mediator it promotes growth and differentiation of T and B lymphocytes, stimulates production of acute-phase proteins by hepatocytes, acts as an endogenous pyrogen [31,38,39] and increases vascular permeability by the enlargement of gaps between endothelial cells [40]. During inflammation and wound healing IL-6 can induce decorin synthesis in sprouting endothelial cells promoting angiogenesis [41]. Its role as an anti- inflammatory cytokine is mediated through activation of IL-1RA and IL-10 or inhibitory effects on TNF-alpha and IL-1beta [42].…”

Regulation of matrix biology by matrix metalloproteinases

“…This suggests that if the fibrillar nature of the collagen I is disrupted, for example by proteolysis, then the production of mature decorin is altered. Thus, decorin production can be regulated by the composition and condition of the ECM [46]. We are just beginning to understand the importance of MMP activity for appropriate regulation of the ECM.…”