LXR, PPAR&amp;lt;i&amp;gt;γ&amp;lt;/i&amp;gt;, and PPAR&amp;lt;i&amp;gt;δ&amp;lt;/i&amp;gt; Agonists Are Not Sufficient to Demonstrate Therapeutic Potential against Mouse Model of Systemic Lupus Erythematosus

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

doi:10.4236/ojra.2017.72012

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.

Highlights

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 facilitate the clearance of apoptotic cells and exert anti-inflammatory effects in systemic lupus erythematosus (SLE)
We investigated the efficacy of LXR agonist (GW3965) or dual treatment of Peroxisome proliferator-activated receptor γ (PPARγ) and PPARδ (GW0742) agonists in SLE animal models, female MRL/MpJ-Fas/J mice and BALB/cAJcl mice treated with pristane
We explored the efficacy of LXR agonist (GW3965) or dual treatment of PPARγ and PPARδ (GW0742) agonists in SLE animal model in mice, female MRL/MpJ-Fas/J miceand BALB/cAJcl mice treated with pristane

Summary

Introduction

PPARγ agonists exert anti-inflammatory and immunomodulatory effects, and the beneficial impacts of rosiglitazone were reported for the amelioration of the autoantibody production, renal disease, and atherosclerosis in MRL-lpr mice depending on the induction of adiponectin [1] and in NZBWF1 mice [2]. Genetic depletion of PPARδ decreased the expression of opsonins such as C1qb and Mertk, which was resulted in the impairment of clearance for apoptotic cells and autoimmune kidney disease resembling lupus nephritis in human [4]. We explored the efficacy of LXR agonist (GW3965) or dual treatment of PPARγ (pioglitazone) and PPARδ (GW0742) agonists in SLE animal model in mice, female MRL/MpJ-Fas/J miceand BALB/cAJcl mice treated with pristane

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Conclusion