title: Klotho Contributes to Pravastatin Effect on Suppressing IL-6 Production in Endothelial Cells.
abstract: Both statins and klotho have been shown to be beneficial in vascular diseases. Interleukin- (IL-) 6 is evidenced as an indicator reflecting the stability of atherosclerotic plaque and involved in the pathogenesis of artery atherosclerosis. However, the relationship between statin, klotho, and IL-6 under an inflammatory environment is unknown. Using primary human umbilical vein endothelial cells (HUVECs), pravastatin dose-dependently induced klotho expression in contrast to remarkable suppression to IL-6 expressions determined by qRT-PCR. Moreover, TNF-α-induced IL-6 was partly but significantly blunted by pravastatin detected by ELISA. To further study the role of klotho in modulating IL-6 expression, endothelial cells with klotho overexpression were treated with TNF-α. Importantly, TNF-α-induced IL-6 production was markedly attenuated in klotho-overexpressed cells. In agreement with in vitro data, a marked reduction of klotho mRNA expression was found in isolated peripheral blood mononuclear cells (PBMCs) from patients with atherosclerosis. Together, these data suggested that pravastatin could suppress IL-6 production via promoting klotho expression in endothelial cells under inflammatory stimuli.
authors.affiliation: Department of Clinical Laboratory, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China; State Key Laboratory of Protein and Plant Gene Research, College of Life Science, Peking University, Beijing 100871, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China.
authors.forename: Zhanjun
authors.identifier: 0000-0002-8282-1587
authors.initials: Z
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, College of Life Science, Peking University, Beijing 100871, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Clinical Laboratory, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing 210029, China.
authors.forename: Hongbing
authors.identifier: 0000-0003-0940-1401
authors.initials: H
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D000090265:Klotho Proteins; D017035:Pravastatin / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005966:Glucuronidase; D000090265:Klotho Proteins; D017035:Pravastatin