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

doi:10.1016/S0008-6363(00)00287-X

Cardiovascular Research 2001 49(4):882-890; doi:10.1016/S0008-6363(00)00287-X
© 2001 by European Society of Cardiology

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

El Mostafa Mtairag^a^,c, Sylvie Chollet-Martin^b, Mounia Oudghiri^c, Nathalie Laquay^a, Marie-Paule Jacob^a, Jean-Baptiste Michel^a and Laurent J. Feldman^a^,*

^aU460 INSERM, X. Bichat School of Medicine, Paris, France
^bImmunology Department and U479 INSERM, Bichat Hospital, Paris, France
^cHassan II University, School of Sciences Ain chok, Department of Biology, Casablanca, Morocco

^* Corresponding author. Tel.: +33-1-4485-6160; fax: +33-1-4485-6157 laurent.feldman{at}bch.ap-hop-paris.fr

Objective: Monocyte adhesion to endothelial cells and subsequentsecretion of matrix metalloproteinases (MMPs) by activated macrophagesare key events in arteriosclerosis and restenosis. We testedthe hypothesis that interleukin-10 (IL-10), a potent anti-inflammatorycytokine, inhibits monocyte-endothelial cell interactions. Methods:The effect of IL-10 on monocyte/endothelial cell adhesion, aswell as on the expression of MMP-9 and the tissue inhibitorof MMP-9, TIMP-1, were first tested in vitro in coculture systems.In addition, we used an ex vivo binding assay to study the inhibitoryeffect of IL-10 on monocyte adhesion to carotid arteries obtainedfrom either normal, or L-nitro arginine-methyl ester (L-NAME)-treatedrats. The effect of IL-10 on the expression of monocyte adhesionmolecules (CD18 and CD62-L) was studied by flow cytometry. Results:IL-10 (150 ng/ml) inhibits monocyte adhesion to endothelialcells (by 35%) and to carotid arteries (by 40 and 50%, in normaland L-NAME-treated rats, respectively), via direct modulationof the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependentlydecreases MMP-9 activity and increases TIMP-1 levels in coculturesystems, both at the transcriptional level. Conclusions: Ourresults suggest that IL-10 is an important modulator of monocyte–endothelialcell interactions.

KEYWORDS Atherosclerosis; Cell culture/isolation; Cytokines; Leukocytes

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