Author(s)

Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Sonia Zeggar, Sumie Hiramatsu, Minglu Yan, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Ken-ei Sada, Jun Wada^*

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

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.

Nuclear Receptors, Liver X Receptor (LXR), Peroxisome Proliferator-Activated Receptor (PPAR), Systemic Lupus Erythematosus (SLE)

Tatebe, N. , Watanabe, K. , Zeggar, S. , Hiramatsu, S. , Yan, M. , Katsuyama, T. , Katsuyama, E. , Watanabe, H. , Sada, K. and Wada, J. (2017) LXR, PPARγ, and PPARδ Agonists Are Not Sufficient to Demonstrate Therapeutic Potential against Mouse Model of Systemic Lupus Erythematosus. Open Journal of Rheumatology and Autoimmune Diseases, 7, 128-136. doi: 10.4236/ojra.2017.72012.