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Peroxisome proliferator-activated receptor gamma agonists in the prevention and
treatment of murine systemic lupus erythematosus
#MMPMID24456224
Aprahamian TR
; Bonegio RG
; Weitzner Z
; Gharakhanian R
; Rifkin IR
Immunology
2014[Jul]; 142
(3
): 363-73
PMID24456224
show ga
Peroxisome proliferator-activated receptor gamma (PPAR?) agonists are known to
have many immunomodulatory effects. We have previously shown that the PPAR?
agonist rosiglitazone is beneficial when used early in prevention of disease in
murine models of systemic lupus erythematosus (SLE) and SLE-related
atherosclerosis. In this report, we demonstrate that another PPAR? agonist,
pioglitazone is also beneficial as a treatment for early murine lupus, indicating
that this is a class effect and not agent-specific. We further attempt to define
the ability of PPAR? agonists to ameliorate established or severe autoimmune
disease using two mouse models: the MRL.lpr SLE model and the gld.apoE(-/-) model
of accelerated atherosclerosis and SLE. We demonstrate that, in contrast to the
marked amelioration of disease seen when PPAR? agonist treatment was started
before disease onset, treatment with rosiglitazone after disease onset in MRL.lpr
or gld.apoE(-/-) mice had minimal beneficial effect on the development of the
autoimmune phenotype; however, rosiglitazone treatment remained highly effective
at reducing lupus-associated atherosclerosis in gld.apoE(-/-) mice after disease
onset or when mice were maintained on a high cholesterol Western diet. These
results suggest that beneficial effects of PPAR? agonists on the development of
autoimmunity might be limited to the early stages of disease, but that
atherosclerosis, a major cause of death in SLE patients, may be ameliorated even
in established or severe disease.
|Animals
[MESH]
|Apolipoproteins E/deficiency/immunology
[MESH]
|Lupus Erythematosus, Systemic/*drug therapy/immunology/*prevention & control
[MESH]
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