Interleukin-19 decreases leukocyte-endothelial cell interactions by reduction in endothelial cell adhesion molecule mRNA stability

Vascular endothelial cell (EC) inflammation is a key event in the pathogenesis of multiple vascular diseases. We tested the hypothesis that interleukin-19 (IL-19), an anti-inflammatory T(h)2 interleukin, could have a direct anti-inflammatory effect on ECs to decrease inflammation. IL-19 can significantly decrease tumor necrosis factor (TNF)-alpha-driven intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mRNA and protein abundance in cultured human coronary artery ECs (P < 0.01). IL-19 treatment of ECs, but not monocytes, significantly reduced monocyte adhesion to EC monolayers (P < 0.01). In vivo, systemic administration of IL-19 could significantly reduce TNF-alpha-induced leukocyte rolling and adhesion in wild-type mice as assayed by intravital microscopy (P < 0.05). IL-19 does not reduce TNF-alpha-stimulated NF-kappa B activation in ECs but does decrease serine phosphorylation and cytoplasmic translocation of the mRNA stability factor HuR and significantly reduces stability of ICAM-1 and VCAM-1 mRNA (P < 0.01). These data are the first to report that IL-19 can reduce leukocyte-endothelial cell adhesion and the first to propose reduction in HuR-mediated mRNA stability of ICAM-1 and VCAM-1 as a mechanism. Expression of IL-19 by ECs may represent a protective mechanism to promote resolution of the vascular response to inflammation. Function of IL-19 outside of the immune system is a novel concept, suggesting that resident vascular cells can adopt a T(h)2 phenotype, and has important ramifications for numerous inflammatory diseases.