Abrogation of skin disease in lupus-prone MRL/Faslpr mice by means of a novel tylophorine analog

Jin Young Choi, Wenli Gao, Tared Odegard, Her Shyong Shiah, Michael Kashgarian, Jennifer M. McNiff, David C. Baker, Yung Chi Cheng, Joseph Craft

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35 Citations (Scopus)

Abstract

Objective. To test the therapeutic effect of DCB-3503, a synthetic compound derived from a natural product that inhibits NF-κB, on end-organ disease in the MRL-Faslpr murine model of systemic lupus erythematosus (SLE). Methods. Eight-week-old female MRI/Faslpr mice were treated intraperitoneally with a low (2 mg/kg) or high (6 mg/kg) dose of DCB-3503 for 10 weeks. Control groups were administered vehicle treatment alone (negative control) or 25 mg/kg cyclopliosphamide (positive control). Mice were bled before (8 weeks) and during (13 weeks) treatment, and when they were killed (20 weeks), and serum samples were analyzed for total IgM and IgG levels and autoantibody titers. When the mice were killed, spleen and lymph nodes (axillary, brachial, and cervical) were examined by flow cytometric analysis. The presence of skin and renal disease was determined by histopathologic analysis. Results. DCB-3503 reduced anti-double-stranded DNA and antichromatin autoantibodies and nearly abrogated inflammatory skin disease in MRL/Fas lpr mice; however, it had little effect on histologic kidney disease. Treated mice did not have hematologic or hepatic toxicity. These data indicate that end-organ disease in MRL/Faslpr mice responds differentially to NF-κB inhibitor. Conclusion. DCB-3503 causes significant abrogation of skin disease in MHL/Faslpr mice and may potentially be beneficial in the treatment of inflammatory skin disease in SLE.

Original languageEnglish
Pages (from-to)3277-3283
Number of pages7
JournalArthritis and Rheumatism
Volume54
Issue number10
DOIs
Publication statusPublished - Oct 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Choi, J. Y., Gao, W., Odegard, T., Shiah, H. S., Kashgarian, M., McNiff, J. M., Baker, D. C., Cheng, Y. C., & Craft, J. (2006). Abrogation of skin disease in lupus-prone MRL/Faslpr mice by means of a novel tylophorine analog. Arthritis and Rheumatism, 54(10), 3277-3283. https://doi.org/10.1002/art.22119