Abstract 457: N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) Prevents The Development Of Nephritis And Skin Lesions In Mouse Model Of Systemic Lupus Erythematosus (MRL/lpr)
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by development of auto antibodies against various self-antigens and deposition of immune complexes leading to inflammation, fibrosis and end organ damage. Ac-SDKP is a naturally occurring tetrapeptide that in hypertension and other diseases such as autoimmune myocarditis prevents inflammation and fibrosis in heart, kidney and vasculature. Here we tested the hypothesis that Ac-SDKP in a mouse model of SLE decreases autoimmune responses, thus preventing inflammation and renal damage. To test this, lupus mice were treated with Ac-SDKP for 20 weeks. Ac-SDKP treated lupus mice exhibited significant decrease in 1) macrophage and T cell infiltration, 2) expression of pro-inflammatory cytokines, 3) complement system activation and 4) expression of cell adhesion protein ICAM-1. In addition, the lupus mice had a significant improvement in renal function (GFR), decrease in glomerular damage and interstitial collagen deposition. Ac-SDKP also reduced the facial skin lesion. Ac-SDKP did not decrease the production of autoantibodies nor blood pressure. Therefore the protective effect of Ac-SDKP is most likely achieved by modulation of the activation of the complement system, expression of chemokines and ICAM-1, leading to a reduction of innate and adaptive immunity cell infiltration in the kidney
Author Disclosures: T. Liao: None. P. Nakagawa: None. B. Janic: None. M. D’Ambrosio: None. M.E. Worou: None. X. Yang: None. N. Rhaleb: None. O.A. Carretero: None.
- © 2014 by American Heart Association, Inc.