PPAR-α Agonist Suppresses Expression of Immune Mediators in B Cells in a Murine Model of Systemic Lupus Erythematosus.

Background/

Objectives

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues.

Methods

The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R+ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643's impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R+ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR.

Results

WY14643 decreased inflammatory markers such as CD45R+IFN-γ+, CD45R+IL-6+, CD45R+iNOS+, CD45R+MCP-1+, CD45R+IL-1α+, CD45R+IL-2+, CD45R+Notch1+, CD45R+Notch3+, CD45R+GITR+, and CD45R+NF-κB p65+ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney.

Conclusions

This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis.