title: Interleukin-19 decreases leukocyte-endothelial cell interactions by reduction in endothelial cell adhesion molecule mRNA stability.
abstract: 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 Th2 interleukin, could have a direct anti-inflammatory effect on ECs to decrease inflammation. IL-19 can significantly decrease tumor necrosis factor (TNF)-α-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-α-induced leukocyte rolling and adhesion in wild-type mice as assayed by intravital microscopy (P < 0.05). IL-19 does not reduce TNF-α-stimulated NF-κB 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 Th2 phenotype, and has important ramifications for numerous inflammatory diseases.
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Ross N
authors.initials: RN
authors.lastname: England
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Preston
authors.forename: Rosario
authors.initials: R
authors.lastname: Scalia
authors.forename: Michael V
authors.initials: MV
authors.lastname: Autieri
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D051959:ELAV Proteins / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology*; D036904:Leukocyte Rolling / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D051959:ELAV Proteins; C568779:ESAM protein, human; C421250:IL19 protein, human; D007378:Interleukins; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: ICAM-1; VCAM-1; endothelial cell; interleukin-19; leukocyte adhesion