Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion

• Published in: Cardiovascular research 2001-03, Vol.49 (4), p.882-890
• Main Authors: Mostafa Mtairag, El, Chollet-Martin, Sylvie, Oudghiri, Mounia, Laquay, Nathalie, Jacob, Marie-Paule, Michel, Jean-Baptiste, Feldman, Laurent J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Biological and medical sciences; Blood vessels and receptors; Blotting, Western; Cell Adhesion - drug effects; Coculture Techniques; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Endothelium, Vascular - metabolism; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Humans; Interleukin-10 - pharmacology; Matrix Metalloproteinase 9 - metabolism; Monocytes - metabolism; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Vertebrates: cardiovascular system
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(00)00287-X

Abstract Objective: Monocyte adhesion to endothelial cells and subsequent secretion of matrix metalloproteinases (MMPs) by activated macrophages are key events in arteriosclerosis and restenosis. We tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, inhibits monocyte-endothelial cell interactions. Methods: The effect of IL-10 on monocyte/endothelial cell adhesion, as well as on the expression of MMP-9 and the tissue inhibitor of MMP-9, TIMP-1, were first tested in vitro in coculture systems. In addition, we used an ex vivo binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to carotid arteries obtained from either normal, or l-nitro arginine-methyl ester (l-NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion molecules (CD18 and CD62-L) was studied by flow cytometry. Results: IL-10 (150 ng/ml) inhibits monocyte adhesion to endothelial cells (by 35%) and to carotid arteries (by 40 and 50%, in normal and l-NAME-treated rats, respectively), via direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependently decreases MMP-9 activity and increases TIMP-1 levels in coculture systems, both at the transcriptional level. Conclusions: Our results suggest that IL-10 is an important modulator of monocyte-endothelial cell interactions.