TITLE:
LXR, PPARγ, and PPARδ Agonists Are Not Sufficient to Demonstrate Therapeutic Potential against Mouse Model of Systemic Lupus Erythematosus
AUTHORS:
Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Sonia Zeggar, Sumie Hiramatsu, Minglu Yan, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Ken-ei Sada, Jun Wada
KEYWORDS:
Nuclear Receptors, Liver X Receptor (LXR), Peroxisome Proliferator-Activated Receptor (PPAR), Systemic Lupus Erythematosus (SLE)
JOURNAL NAME:
Open Journal of Rheumatology and Autoimmune Diseases,
Vol.7 No.2,
May
31,
2017
ABSTRACT: 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.