title: Interferon regulator factor 1/retinoic inducible gene I (IRF1/RIG-I) axis mediates 25-hydroxycholesterol-induced interleukin-8 production in atherosclerosis.
abstract: OBJECTIVE
  In this study, the role of retinoic inducible gene I (RIG-I)-mediated signalling in the inflammation of atherosclerosis was investigated to explain the pathology of atherosclerosis.
  
  
  RESULTS
  Human and mouse primary cells were exposed to 25-hydroxycholesterol followed by examination of gene expression and activation of the signal pathway with biochemical and molecular biological techniques. A mouse atherosclerotic model was also used. We found that RIG-I was induced in macrophages and endothelium by 25-hydroxycholesterol. Interferon regulatory factor 1 is a key transcription factor for the induction of RIG-I by 25-hydroxycholesterol. The induction of interleukin-8 and growth-regulated protein α, the mouse interleukin-8 homologue, by 25-hydroxycholesterol is mediated by RIG-I signalling. RIG-I transduces the signal to downstream molecules, mitochondrial antiviral-signalling protein, transforming growth factor-β-activated kinase 1, and mitogen-activated protein kinase, leading to the activation of nuclear factor κB, activator protein-1, and nuclear factor interleukin-6, all of which are required for the expression of interleukin-8. Finally, we observed that RIG-I is highly expressed in atherosclerotic lesions.
  
  
  CONCLUSIONS
  Our data demonstrate that RIG-I signalling mediates atherosclerotic inflammation. Targeting RIG-I signalling should provide a way to inhibit atherosclerotic inflammation, which holds potential for the therapy of atherosclerosis.
authors: State Key Laboratory of Protein and Plant Gene Research, College of Life Science, Peking University, Beijing, China.
authors: Feng
authors: F
authors: Wang
authors: Weiwei
authors: W
authors: Xia
authors: Feng
authors: F
authors: Liu
authors: Ji
authors: J
authors: Li
authors: Guang
authors: G
authors: Wang
authors: Jun
authors: J
authors: Gu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D054360:Chemokine CXCL1 / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D050856:Interferon Regulatory Factor-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D001057:Apolipoproteins E; D054360:Chemokine CXCL1; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D006888:Hydroxycholesterols; D050856:Interferon Regulatory Factor-1; D016209:Interleukin-8; D020930:MAP Kinase Kinase Kinases; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D000099151:MAP Kinase Kinase Kinase 7; C508606:CXCL8 protein, human; C494257:IRF1 protein, human; C494258:Irf1 protein, mouse; C007997:25-hydroxycholesterol; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse