Print Email Facebook Twitter Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis Title Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis Author Burger-Kentischer, A. Goebel, H. Seiler, R. Fraedrich, G. Schaefer, H.E. Dimmeler, S. Kleemann, R. Bernhagen, J. Ihling, C. Gaubius Instituut TNO Publication year 2002 Abstract Background - Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), a cytokine with potent inflammatory functions, was thus considered to be important in atherosclerotic lesion evolution. Methods and Results - We studied the presence and distribution of MIF immunoreactivity (MIF-IR) and MIF mRNA in internal mammary arteries with a normal histology and arteries with plaques in different stages of human atherosclerosis. To address a potential role for the coactivator Jab1 as a cellular mediator of MIF effects in vascular tissue, we correlated the expression of MIF to that of Jab1 by using immunohistochemistry and coimmunoprecipitation. We further sought to determine a potential functional role for endothelium-derived MIF in early atherogenesis by studying the effects of oxidized LDL on MIF expression in cultured human umbilical vascular endothelial cells. The results showed that MIF-IR and Jab1-IR are found in all cell types present in atherosclerotic lesions, that MIF-IR is upregulated during progression of atherosclerosis, that MIF is produced locally in the arterial wall, and that all MIF+ cells are simultaneously Jab1 +. Coimmunoprecipitation experiments demonstrated in vivo complex formation between MIF and Jab1 in plaques. MIF expression in human umbilical vascular endothelial cells and a macrophage line was upregulated after stimulation with oxidized LDL. Conclusions - MIF is produced abundantly by various cells in all types of human atherosclerotic lesions and thus may play an important role in early plaque development and advanced complicated lesions. MIF-Jab1 complexes could serve critical regulatory functions in atherosclerotic lesion evolution. Chemicals/CAS: COPS5 protein, human, EC 3.4.-.-; DNA-Binding Proteins; Intracellular Signaling Peptides and Proteins; Lipoproteins, LDL; Macrophage Migration-Inhibitory Factors; oxidized low density lipoprotein; Peptide Hydrolases, EC 3.4.-; Transcription Factors Subject Aortic DiseasesArteriosclerosisCarotid Artery DiseasesCells, CulturedCoronary ArteriosclerosisDisease ProgressionDNA-Binding ProteinsEndothelium, VascularFibrosisHumansImmunohistochemistryInflammationIntracellular Signaling Peptides and ProteinsLipoproteins, LDLMacrophage Migration-Inhibitory FactorsMacrophagesMammary ArteriesPeptide HydrolasesTranscription FactorsTranscription, GeneticUp-Regulation To reference this document use: http://resolver.tudelft.nl/uuid:48c35665-831a-4ac9-8bef-bcf5f6354f61 DOI https://doi.org/10.1161/01.cir.0000012942.49244.82 TNO identifier 236510 ISSN 0009-7322 Source Circulation, 105 (13), 1561-1566 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.