OBJECTIVE: In present study, we employed cDNA-based microarray technique to investigate the effect of a synthetic LXR ligand T0901317 on hepatic gene expression of proinflammatory cytokines in apolipoprotein E knockout mice fed an atherogenic diet. METHODS AND RESULTS: Male 8-week-old apoE-/- mice were randomly divided into four groups, baseline group, vehicle group, prevention group and treatment group. All of the mice were fed a high-fat/high-cholesterol diet with or without LXR agonist T0901317 for 8 or 14 weeks. Gene array analysis found 17 atherosclerosis-related genes with a 2- to 8-fold difference in expression level between vehicle-treated group and T0901317-treated group. It induced mRNA expression of proinflammatory cytokine tumor necrosis factor (TNF), but inhibited gene expression of several other proinflammatory cytokines including interleukin (IL)-1alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix metalloproteinase-9, IL-1alpha, IL-6, and IL-7 were verified by real-time quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up-regulation of TNFalpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels in plasma sample. CONCLUSION: The synthetic LXR agonist T0901317 has paradoxical roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.
OBJECTIVE: In present study, we employed cDNA-based microarray technique to investigate the effect of a synthetic LXR ligand T0901317 on hepatic gene expression of proinflammatory cytokines in apolipoprotein E knockout mice fed an atherogenic diet. METHODS AND RESULTS: Male 8-week-old apoE-/- mice were randomly divided into four groups, baseline group, vehicle group, prevention group and treatment group. All of the mice were fed a high-fat/high-cholesterol diet with or without LXR agonist T0901317 for 8 or 14 weeks. Gene array analysis found 17 atherosclerosis-related genes with a 2- to 8-fold difference in expression level between vehicle-treated group and T0901317-treated group. It induced mRNA expression of proinflammatory cytokine tumor necrosis factor (TNF), but inhibited gene expression of several other proinflammatory cytokines including interleukin (IL)-1alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix metalloproteinase-9, IL-1alpha, IL-6, and IL-7 were verified by real-time quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up-regulation of TNFalpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels in plasma sample. CONCLUSION: The synthetic LXR agonist T0901317 has paradoxical roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.
Authors: G Pasterkamp; A H Schoneveld; D J Hijnen; D P de Kleijn; H Teepen; A C van der Wal; C Borst Journal: Atherosclerosis Date: 2000-06 Impact factor: 5.162
Authors: J Lee; W H Ho; M Maruoka; R T Corpuz; D T Baldwin; J S Foster; A D Goddard; D G Yansura; R L Vandlen; W I Wood; A L Gurney Journal: J Biol Chem Date: 2001-01-12 Impact factor: 5.157
Authors: M Piecyk; S Wax; A R Beck; N Kedersha; M Gupta; B Maritim; S Chen; C Gueydan; V Kruys; M Streuli; P Anderson Journal: EMBO J Date: 2000-08-01 Impact factor: 11.598
Authors: Sylvie Marleau; Diala Harb; Kim Bujold; Roberta Avallone; Khadija Iken; Yanfei Wang; Annie Demers; Martin G Sirois; Maria Febbraio; Roy L Silverstein; André Tremblay; Huy Ong Journal: FASEB J Date: 2005-08-25 Impact factor: 5.191
Authors: Florian Blaschke; Yasunori Takata; Evren Caglayan; Alan Collins; Peter Tontonoz; Willa A Hsueh; Rajendra K Tangirala Journal: Circ Res Date: 2006-11-16 Impact factor: 17.367
Authors: Nancy Levin; Eric D Bischoff; Chris L Daige; Diane Thomas; Calvin T Vu; Richard A Heyman; Rajendra K Tangirala; Ira G Schulman Journal: Arterioscler Thromb Vasc Biol Date: 2004-11-11 Impact factor: 8.311
Authors: Erik R Nelson; Carolyn D DuSell; Xiaojuan Wang; Matthew K Howe; Glenda Evans; Ryan D Michalek; Michihisa Umetani; Jeffrey C Rathmell; Sundeep Khosla; Diane Gesty-Palmer; Donald P McDonnell Journal: Endocrinology Date: 2011-09-20 Impact factor: 4.736
Authors: Jwa van der Hoorn; D Lindén; U Lindahl; Mea Bekkers; M Voskuilen; R Nilsson; J Oscarsson; El Lindstedt; Hmg Princen Journal: Br J Pharmacol Date: 2011-04 Impact factor: 8.739
Authors: María Jose Míguez; John E Lewis; Vaughn E Bryant; Rhonda Rosenberg; Ximena Burbano; Joel Fishman; Deshratn Asthana; Rui Duan; Nair Madhavan; Robert M Malow Journal: J Int AIDS Soc Date: 2010-07-13 Impact factor: 5.396
Authors: Robert Kleemann; Svetlana Bureeva; Ally Perlina; Jim Kaput; Lars Verschuren; Peter Y Wielinga; Eva Hurt-Camejo; Yuri Nikolsky; Ben van Ommen; Teake Kooistra Journal: BMC Syst Biol Date: 2011-08-12