Induction of MIF expression by oxidized LDL via activation of NF-kappaB in vascular smooth muscle cells

Autor: Lihong Chen, Qing Gu, NanpingWang, Guangrui Yang, Jing Wu, Mingfen Wei, Yi Zhu, Jichun Yang, Youfei Guan, Xiaoyan Zhang
Rok vydání: 2009
Předmět:
Male
Vascular smooth muscle
animal diseases
medicine.medical_treatment
Muscle
Smooth
Vascular
chemistry.chemical_compound
Mice
NF-KappaB Inhibitor alpha
Myocyte
Cloning
Molecular
Promoter Regions
Genetic
Cells
Cultured
NF-kappa B
Transfection
respiratory system
Up-Regulation
Intramolecular Oxidoreductases
Lipoproteins
LDL
Cytokine
Female
I-kappa B Proteins
Rabbits
Signal transduction
Cardiology and Cardiovascular Medicine
Signal Transduction
Transcriptional Activation
medicine.medical_specialty
Molecular Sequence Data
Myocytes
Smooth Muscle
chemical and pharmacologic phenomena
Biology
Downregulation and upregulation
Internal medicine
otorhinolaryngologic diseases
medicine
Animals
Humans
Amino Acid Sequence
RNA
Messenger
Macrophage Migration-Inhibitory Factors
Binding Sites
NF-κB
Atherosclerosis
Molecular biology
biological factors
Disease Models
Animal
Endocrinology
chemistry
Macrophage migration inhibitory factor
Zdroj: Atherosclerosis. 207(2)
ISSN: 1879-1484
Popis: Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine playing important roles in atherosclerosis. MIF gene deficiency and neutralizing antibodies against MIF have been reported to exert anti-atherosclerotic effects in various animal models. However, the mechanism by which MIF is induced in atherosclerotic lesions remains unclear. In the present studies, we cloned a 540bp full-length rabbit MIF cDNA by screening a rabbit uterine library. The cDNA contains a 348bp open-reading frame which encodes a deduced 115-amino acid polypeptide with approximately 90% similarity to human and mouse homologs. Constitutive MIF mRNA expression was detected in most rabbit tissues including aortas. The expression of MIF obviously abounded in vascular smooth muscle cells (VSMCs) of the atherosclerotic plaques. In cultured VSMCs, MIF expression was significantly induced by a pro-atherogenic factor, oxidized low-density lipoprotein (oxLDL). Promoter analysis showed there were two NF-kappaB binding sites in the MIF proximal promoter region. Deletion or mutation of the two sites abolished oxLDL-enhanced MIF promoter activity. Moreover, the induction of MIF by oxLDL can be blocked by IkappaB-alpha overexpression. Taken together, our results revealed that MIF expression can be induced by oxLDL in VSMCs via a NF-kappaB dependent manner, which may contribute to the pathogenesis of atherosclerosis.
Databáze: OpenAIRE
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