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-acetylgalactosa mine glycosaminoglycans, e.g., chondroitin sulfate (CS), release the 6 7-kDa elastin binding protein (EBP) from arterial smooth muscle cell ( SMC) surfaces. This disrupts cell contact with elastin, impairs assemb ly 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 m yocytes related to a functional interplay between EBP and the interleu kin-1 receptor type I. We showed that CS-induced shedding of the EBP o r internalization of this receptor after saturation with elastin-deriv ed peptides (kappa-elastin, kappa-El) stimulated fibronectin productio n in cultures of coronary artery SMC to a level observed with recombin ant interleukin (IL)-1 beta. Upregulation of fibronectin by CS or kapp a-El was abolished by a soluble IL-1 receptor antagonist, and synergis tic stimulation of fibronectin production occurred when CS or kappa-El was added with IL-1 beta. 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 c ell surface increased binding of radiolabeled IL-1 beta to CA SMC. We propose a unique interaction between both receptors in which unoccupie d EBP interferes with IL-1 beta binding. Conversely, increased accumul ation of N-acetylgalactosamine glycosaminoglycans or elastin-derived p eptides in the vascular wall may unmask IL-1 receptor type I and incre ase binding of the cytokine and consequent upregulation of fibronectin production. (C) 1996 Academic Press, Inc.