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Antiinflammatory properties of a peptide derived from interleukin-4.

Authors: Klementiev, B  Enevoldsen, MN  Li, S  Carlsson, R  Liu, Y  Issazadeh-Navikas, S  Bock, E  Berezin, V 
Citation: Klementiev B, etal., Cytokine. 2013 Oct;64(1):112-21. doi: 10.1016/j.cyto.2013.07.016. Epub 2013 Aug 20.
Pubmed: (View Article at PubMed) PMID:23972727
DOI: Full-text: DOI:10.1016/j.cyto.2013.07.016

Interleukin-4 (IL-4) is a potent antiinflammatory cytokine. However its use in the clinic is hampered by side effects. We here describe the identification of a novel synthetic peptide, termed Ph8, derived from alpha-helix C of IL-4, which interacts with IL-4 receptor alpha (IL-4Ralpha). Employing various cultured genetically engineered cell lines and primary lymphocytes, surface plasmon resonance, qPCR, ELISA and immunoblotting techniques we found that Ph8 bound IL-4Ralpha and mimicked the anti-inflammatory effects of IL-4 by inhibiting TNF-alpha production by macrophages in vitro. It induced phosphorylation of STAT6 65kD but inhibited phosphorylation of STAT6 110 kD induced by IL-4 in a B-cell line that expressed the type I receptor. It also inhibited the IL-4-stimulated expression of a STAT6-inducible reporter gene in cells that expressed the type II receptor. Ph8 inhibited the proliferation of Th1/2 cells and downregulated the production of IFN-gamma in stimulated Th1 cells. Moreover, Ph8 did not induce any shift in Th1/Th2 profile. This is a favorable effect and it is indicating that Ph8 could block general T cell activation and inflammatory responses without further inducing the side effects generally associated with IL-4 signaling. These data collectively show that Ph8 is only a partial agonist of IL-4 mimicking its desirable properties. In agreement, Ph8 treatment of rats with collagen-induced arthritis, a Th1- and antibody- mediated disease of joint, delayed the manifestation of chronic inflammation and reduced acute inflammation in carrageenan-induced edema. Our findings indicate that Ph8 is a promising potential drug candidate for the treatment of inflammatory diseases.

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CRRD Object Information
CRRD ID: 10402790
Created: 2015-10-29
Species: All species
Last Modified: 2015-10-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.