Functional interplay between interleukin-1 receptor and elastin binding protein regulates fibronectin production in coronary artery smooth muscle cells.
We have previously shown that free galactosugars and N-acetylgalactosamine glycosaminoglycans, e.g., chondroitin sulfate (CS), release the 67-kDa elastin binding protein (EBP) from arterial smooth muscle cell (SMC) surfaces. This disrupts cell contact with elastin, impairs assembly of new elastic fibers, and increases fibronectin production, all of which promote SMC migration and intimal thickening. The present study uncovered a mechanism regulating fibronectin production in vascular myocytes related to a functional interplay between EBP and the interleukin-1 receptor type I. We showed that CS-induced shedding of the EBP or internalization of this receptor after saturation with elastin-derived peptides (kappa-elastin, kappa-El) stimulated fibronectin production in cultures of coronary artery SMC to a level observed with recombinant interleukin (IL)-1beta. Upregulation of fibronectin by CS or kappa-El was abolished by a soluble IL-1 receptor antagonist, and synergistic stimulation of fibronectin production occurred when CS or kappa-El was added with IL-1beta. Immunohistochemistry showed that EBP and IL-1 receptor type I codistributed on surfaces of unstimulated coronary artery SMC, while CS- and kappa-El-dependent removal of EBP from the cell surface increased binding of radiolabeled IL-1beta to CA SMC. We propose a unique interaction between both receptors in which unoccupied EBP interferes with IL-1beta binding. Conversely, increased accumulation of N-acetylgalactosamine glycosaminoglycans or elastin-derived peptides in the vascular wall may unmask IL-1 receptor type I and increase binding of the cytokine and consequent upregulation of fibronectin production.
Hinek
A
A
Division of Cardiovascular Research, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Molossi
S
S
Rabinovitch
M
M
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D013552:Swine; D015854:Up-Regulation
D005353:Fibronectins; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; C054901:elastin-binding proteins; D004549:Elastin; D000116:Acetylgalactosamine