Interleukin (IL)-6 and IL-10 induce decorin mRNA in endothelial cells, but interaction with fibrillar collagen is essential for its translation.
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 alpha(1) or alpha(2) integrins or the alpha(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.
Strazynski
Marco
M
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster and University Hospital Münster, D-48129 Münster, Germany.
Eble
Johannes A
JA
Kresse
Hans
H
Schönherr
Elke
E
D002460:Cell Line; D018920:Coculture Techniques; D003435:Crotalid Venoms / Q000494:pharmacology; D017931:DNA Primers; D058575:Decorin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects*; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
D003435:Crotalid Venoms; C546878:DCN protein, human; D017931:DNA Primers; D058575:Decorin; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D016023:Integrins; D015850:Interleukin-6; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C119730:rhodocetin; D016753:Interleukin-10