Antiinflammatory properties of a peptide derived from interleukin-4
(2013) In Cytokine 64(1). p.112-121- Abstract
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 α-helix C of IL-4, which interacts with IL-4 receptor α (IL-4Rα). Employing various cultured genetically engineered cell lines and primary lymphocytes, surface plasmon resonance, qPCR, ELISA and immunoblotting techniques we found that Ph8 bound IL-4Rα and mimicked the anti-inflammatory effects of IL-4 by inhibiting TNF-α production by macrophages in vitro. It induced phosphorylation of STAT6 65. kD 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... (More)
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 α-helix C of IL-4, which interacts with IL-4 receptor α (IL-4Rα). Employing various cultured genetically engineered cell lines and primary lymphocytes, surface plasmon resonance, qPCR, ELISA and immunoblotting techniques we found that Ph8 bound IL-4Rα and mimicked the anti-inflammatory effects of IL-4 by inhibiting TNF-α production by macrophages in vitro. It induced phosphorylation of STAT6 65. kD 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-γ 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.
(Less)
- author
- Klementiev, Boris ; Enevoldsen, Maj N. ; Li, Shizhong ; Carlsson, Robert LU ; Liu, Yawei ; Issazadeh-Navikas, Shohreh ; Bock, Elisabeth and Berezin, Vladimir
- publishing date
- 2013-10-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Collagen-induced arthritis, Interferon-γ, Interleukin-4, Signalling, Tumor necrosis factor-α
- in
- Cytokine
- volume
- 64
- issue
- 1
- pages
- 10 pages
- publisher
- Academic Press
- external identifiers
-
- scopus:84883519704
- pmid:23972727
- ISSN
- 1043-4666
- DOI
- 10.1016/j.cyto.2013.07.016
- language
- English
- LU publication?
- no
- id
- 267753aa-8b6f-4074-b147-35bb87f25251
- date added to LUP
- 2019-07-02 10:06:50
- date last changed
- 2024-01-16 06:12:32
@article{267753aa-8b6f-4074-b147-35bb87f25251,
abstract = {{<p>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 α-helix C of IL-4, which interacts with IL-4 receptor α (IL-4Rα). Employing various cultured genetically engineered cell lines and primary lymphocytes, surface plasmon resonance, qPCR, ELISA and immunoblotting techniques we found that Ph8 bound IL-4Rα and mimicked the anti-inflammatory effects of IL-4 by inhibiting TNF-α production by macrophages in vitro. It induced phosphorylation of STAT6 65. kD 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-γ 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.</p>}},
author = {{Klementiev, Boris and Enevoldsen, Maj N. and Li, Shizhong and Carlsson, Robert and Liu, Yawei and Issazadeh-Navikas, Shohreh and Bock, Elisabeth and Berezin, Vladimir}},
issn = {{1043-4666}},
keywords = {{Collagen-induced arthritis; Interferon-γ; Interleukin-4; Signalling; Tumor necrosis factor-α}},
language = {{eng}},
month = {{10}},
number = {{1}},
pages = {{112--121}},
publisher = {{Academic Press}},
series = {{Cytokine}},
title = {{Antiinflammatory properties of a peptide derived from interleukin-4}},
url = {{http://dx.doi.org/10.1016/j.cyto.2013.07.016}},
doi = {{10.1016/j.cyto.2013.07.016}},
volume = {{64}},
year = {{2013}},
}