The role of apoptosis in the ameliorating effects of a CDR1-based peptide on lupus manifestations in a mouse model

Amir Sharabi, Dror Luger, Hava Ben-David, Molly Dayan, Heidey Zinger, Edna Mozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Experimental systemic lupus erythematosus (SLE) can be induced in mice following immunization with an anti-DNA mAb expressing a major Id, 16/6Id. Treatment with a peptide, designated human CDR1 (hCDR1; Edratide), that is based on the sequence of CDR1 of the 16/6Id ameliorated disease manifestations. In the present study, we investigated the roles of apoptosis and related molecules in BALB/c mice with induced experimental SLE following treatment with hCDR1. A higher state of activation and increased rate of apoptosis were found in lymphocytes of SLE-afflicted mice as compared with healthy controls. The latter effects were associated with up-regulated caspase-8 and caspase-3, and down-regulated Bcl-xL. The ameliorative effects of hCDR1 were associated with down-regulation of caspase-8 and caspase-3, up-regulation of Bcl-xL, and a reduced rate of apoptosis. Treatment of diseased mice with an apoptosis-reducing compound that inhibited caspases down-regulated the secretion of the pathogenic cytokine IFN-γ and lowered the intensity of glomerular immune complex deposits and the levels of proteinuria. Furthermore, coincubation of Bcl-xL inhibitors with hCDR1-treated cells abrogated the ability of hCDR1 to reduce the activation state of lymphocytes and to down-regulate the secretion of IL-10 and IFN-γ. Moreover, the Bcl-x L-expressing CD4+CD25+ cells from hCDR1-treated mice induced the expression of Bcl-xL in CFSE-labeled CD4 +CD25- cells of the SLE-afflicted mice. Thus, the reduction of apoptosis and the up-regulation of Bcl-xL, which plays an apparent role in tolerance induction, contribute to at least part of the beneficial effects of hCDR1 on lupus manifestations.

Original languageEnglish
Pages (from-to)4979-4987
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - 15 Oct 2007
Externally publishedYes


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