QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jpet.107.123257v1 322/2/879    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kobayashi, N. Articles by Siahaan, T. J. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, N. Articles by Siahaan, T. J.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Antigen-Specific Suppression of Experimental Autoimmune Encephalomyelitis by a Novel Bifunctional Peptide Inhibitor

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas (N.K., H.K., T.J.S.); and Admunex Therapeutics Inc., Sunnyvale, California (L.G., T.M.)

The objective of this study is to evaluate the activity of a novel peptide, i.e., bifunctional peptide inhibitor (BPI), which targets the immunological synapse and inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP_139–151) and an intercellular adhesion molecule-1-binding peptide derived from _L integrin (CD11a_237–246), via a spacer peptide. The therapeutic effect of PLP-BPI was studied in experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice as a model for human multiple sclerosis. Mice that received i.v. injections of PLP-BPI showed significantly lower EAE disease scores and incidence than those treated with vehicle, PLP_139–151 peptide only, CD11a_237–246 peptide only, unlinked mixture of PLP_139–151, and CD11a_237–246 peptides, or other control peptides. Multiple injections of antigenic peptide can produce anaphylactic responses; interestingly, PLP-BPI-treated animals have significantly lower anaphylactic response than do the PLP_139–151-treated group. Therefore, PLP-BPI can effectively inhibit the disease severity and incidence of EAE with a lower possibility of inducing fatal anaphylaxis. These results suggest that BPI-type molecules can be used to treat different autoimmune diseases in which antigenic epitopes have been identified.

Address correspondence to: Dr. Teruna J. Siahaan, Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave, Lawrence, KS 66047-3729. E-mail: siahaan{at}ku.edu

This article has been cited by other articles:

				Y.-H. Lee, Y. Ishida, M. Rifa'i, Z. Shi, K.-i. Isobe, and H. Suzuki Essential Role of CD8+CD122+ Regulatory T Cells in the Recovery from Experimental Autoimmune Encephalomyelitis J. Immunol., January 15, 2008; 180(2): 825 - 832. [Abstract] [Full Text] [PDF]