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- Title
WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease.
- Authors
Archer, D. C.; Frkanec, J. T.; Cromwell, J.; Clopton, P.; Cunard, R.
- Abstract
Peroxisome proliferator-activated receptor alpha (PPARα) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0·05% WY14,643 or control food and immunized with the non-collagenous domain of the α3 chain of Type IV collagen [α3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARα ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80+ macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARα ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-γ mRNA expression in the WY14,643-fed mice, suggesting that the PPARα ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARα ligands may be a novel treatment for inflammatory renal disease.
- Subjects
COORDINATION compounds; LIGANDS (Biochemistry); PEROXISOMES; MICROBODIES; GLOMERULONEPHRITIS; MEMBRANE disorders; THERAPEUTICS
- Publication
Clinical & Experimental Immunology, 2007, Vol 150, Issue 2, p386
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2007.03505.x