Antiinflammatory properties of a peptide derived from interleukin-4

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Antiinflammatory properties of a peptide derived from interleukin-4. / Klementiev, Boris; Enevoldsen, Maj N; Li, Shizhong; Carlsson, Robert; Liu, Yawei; Navikas, Shohreh; Bock, Elisabeth; Berezin, Vladimir.

I: Cytokine, Bind 64, Nr. 1, 10.2013, s. 112-21.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Klementiev, B, Enevoldsen, MN, Li, S, Carlsson, R, Liu, Y, Navikas, S, Bock, E & Berezin, V 2013, 'Antiinflammatory properties of a peptide derived from interleukin-4', Cytokine, bind 64, nr. 1, s. 112-21. https://doi.org/10.1016/j.cyto.2013.07.016

APA

Klementiev, B., Enevoldsen, M. N., Li, S., Carlsson, R., Liu, Y., Navikas, S., ... Berezin, V. (2013). Antiinflammatory properties of a peptide derived from interleukin-4. Cytokine, 64(1), 112-21. https://doi.org/10.1016/j.cyto.2013.07.016

Vancouver

Klementiev B, Enevoldsen MN, Li S, Carlsson R, Liu Y, Navikas S o.a. Antiinflammatory properties of a peptide derived from interleukin-4. Cytokine. 2013 okt;64(1):112-21. https://doi.org/10.1016/j.cyto.2013.07.016

Author

Klementiev, Boris ; Enevoldsen, Maj N ; Li, Shizhong ; Carlsson, Robert ; Liu, Yawei ; Navikas, Shohreh ; Bock, Elisabeth ; Berezin, Vladimir. / Antiinflammatory properties of a peptide derived from interleukin-4. I: Cytokine. 2013 ; Bind 64, Nr. 1. s. 112-21.

Bibtex

@article{e8b3ef5090d4412cabbad507f913bb5e,
title = "Antiinflammatory properties of a peptide derived from interleukin-4",
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 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-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.",
keywords = "Animals, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Experimental, Cell Proliferation, Edema, HEK293 Cells, Humans, Interferon-gamma, Interleukin-4, Interleukin-4 Receptor alpha Subunit, Lymphocyte Activation, Macrophage Activation, Macrophages, Male, Mice, Mice, Inbred C57BL, Peptide Fragments, Phosphorylation, Protein Binding, Rats, Rats, Wistar, STAT6 Transcription Factor, Th1 Cells, Tumor Necrosis Factor-alpha",
author = "Boris Klementiev and Enevoldsen, {Maj N} and Shizhong Li and Robert Carlsson and Yawei Liu and Shohreh Navikas and Elisabeth Bock and Vladimir Berezin",
note = "Copyright {\circledC} 2013 Elsevier Ltd. All rights reserved.",
year = "2013",
month = "10",
doi = "10.1016/j.cyto.2013.07.016",
language = "English",
volume = "64",
pages = "112--21",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press",
number = "1",

}

RIS

TY - JOUR

T1 - Antiinflammatory properties of a peptide derived from interleukin-4

AU - Klementiev, Boris

AU - Enevoldsen, Maj N

AU - Li, Shizhong

AU - Carlsson, Robert

AU - Liu, Yawei

AU - Navikas, Shohreh

AU - Bock, Elisabeth

AU - Berezin, Vladimir

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/10

Y1 - 2013/10

N2 - 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 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-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.

AB - 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 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-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.

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Arthritis, Experimental

KW - Cell Proliferation

KW - Edema

KW - HEK293 Cells

KW - Humans

KW - Interferon-gamma

KW - Interleukin-4

KW - Interleukin-4 Receptor alpha Subunit

KW - Lymphocyte Activation

KW - Macrophage Activation

KW - Macrophages

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Peptide Fragments

KW - Phosphorylation

KW - Protein Binding

KW - Rats

KW - Rats, Wistar

KW - STAT6 Transcription Factor

KW - Th1 Cells

KW - Tumor Necrosis Factor-alpha

U2 - 10.1016/j.cyto.2013.07.016

DO - 10.1016/j.cyto.2013.07.016

M3 - Journal article

VL - 64

SP - 112

EP - 121

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 1

ER -

ID: 108143264