N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus
Recommended Citation
Liao TD, Nakagawa P, Janic B, D'Ambrosio MA, Worou ME, Peterson EL, Rhaleb NE, Yang XP, Carretero OA. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus. Am J Physiol Renal Physiol. 2015;308(10):F1146-54.
Document Type
Article
Publication Date
5-15-2015
Publication Title
American journal of physiology. Renal physiology
Abstract
Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system.
Medical Subject Headings
Animals; Cell Movement; Complement System Proteins; Cytokines; Disease Models, Animal; Female; Glomerular Filtration Rate; Intercellular Adhesion Molecule-1; Lupus Erythematosus, Systemic; Lupus Nephritis; Mice; Mice, Inbred MRL lpr; Oligopeptides; T-Lymphocytes
PubMed ID
25740596
Volume
308
Issue
10
First Page
1146
Last Page
1154
