LXR, PPAR<i>γ</i>, and PPAR<i>δ</i>Agonists Are Not Sufficient to Demonstrate Therapeutic Potential against Mouse Model of Systemic Lupus Erythematosus

• 作者: Eri Katsuyama Haruki Watanabe Jun Wada Katsue Sunahori Watanabe Ken-ei Sada Minglu Yan Noriko Toyota Tatebe Sonia Zeggar Sumie Hiramatsu Takayuki Katsuyama
• 来源期刊: 风湿病与自身免疫疾病期刊(英文)
• 学科: 医学
• 关键词: Nuclear Receptors Liver X RECEPTOR (LXR) PEROXISOME Proliferator-Activated RECEPTOR (PPAR) Systemic Lupus Erythematosus (SLE)
• 年，卷（期）: 2017,（2）
• 页码范围: 128-136
• 页数: 9页
• 分类号: R5

摘要

Aim: We aimed to investigate whether the agonists for liver X receptor (LXR) ameliorate lupus-like phenotypes in mice mediated by the clearance of apoptotic cells, and compare with peroxisome proliferator-activated receptor (PPAR) γ plus PPARδ agonists, which also facilitate the clearance of apoptotic cells and exert anti-inflammatory effects in systemic lupus erythematosus (SLE). Methods: We investigated the efficacy of LXR agonist (GW3965) or dual treatment of PPARγ (pioglitazone) and PPARδ (GW0742) agonists in SLE animal models, female MRL/MpJ-Fas/J mice and BALB/cAJcl mice treated with pristane. The data were analyzed with one-way analysis of variance and Tukey’s honestly significant difference tests. Results: The treatment with LXR or PPARγ/δ agonists did not significantly alter the swelling of lymph nodes, ds-DNA production, albuminuria, histological score of glomerular lesions, and mRNA expression of target genes including Abca1, C1qa, Icam1, Mertk and Tnf. Conclusion: LXR or PPARγ/δ agonists targeting the impaired clearance for apoptosis cells may not be efficient in the remission induction therapy in SLE.