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Bifunctional Peptide Inhibitors Suppress Interleukin-6 Proliferation and Ameliorates Murine Collagen-Induced Arthritis
Buyuktimkin, Barlas ; Kiptoo, Paul ; Siahaan, Teruna J.
Buyuktimkin, Barlas
Kiptoo, Paul
Siahaan, Teruna J.
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Abstract
The objective of this study is to evaluate the efficacy and potential mechanism of action of type-II collagen
bifunctional peptide inhibitor (CII-BPI) molecules in suppressing rheumatoid arthritis in the collagen-induced arthritis
(CIA) mouse model. CII-BPI molecules (CII-BPI-1, CII-BPI-2, and CII-BPI-3) were formed through conjugation
between an antigenic peptide derived from type-II collagen and a cell adhesion peptide LABL (CD11a237-246) from
the I-domain of LFA-1 via a linker molecule. The hypothesis is that the CII-BPI molecules simultaneously bind to
MHC-II and ICAM-1 on the surface of APC and block maturation of the immunological synapse. As a result, the
differentiation of naïve T cells is altered from inflammatory to regulatory and/or suppressor T cells. The efficacies of
CII-BPI molecules were evaluated upon intravenous injections in CIA mice. Results showed that CII-BPI-1 and CIIBPI-
2 suppressed the joint inflammations in CIA mice in a dose-dependent manner and were more potent than the
respective antigenic peptides alone. CII-BPI-3 was not as efficacious as CII-BPI-1 and CII-BPI-2. Significantly less
joint damage was observed in CII-BPI-2 and CII-2 treated mice than in the control. The production of IL-6 was
significantly lower at the peak of disease in mice treated with CII-BPI-2 compared to those treated with CII-2 and
control. In conclusion, this is the first proof-of-concept study showing that BPI molecules can be used to suppress
RA and may be a potential therapeutic strategy for the treatment of rheumatoid arthritis.
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This is the published version. Copyright 2014 OMICS International
Date
2014-11
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OMICS International
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Büyüktimkin B, Kiptoo P, Siahaan TJ (2014) Bifunctional Peptide Inhibitors Suppress Interleukin-6 Proliferation and Ameliorates Murine Collagen-Induced Arthritis. J Clin Cell Immunol 5: 273. doi:10.4172/2155-9899.1000273.