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Identification and characterization of a novel IL-4 receptor α chain (IL-4Rα) antagonist to inhibit IL-4 signalling

Ahmed, Nayyar, Dhanapala, Pathum and Suphioglu, Cenk 2015, Identification and characterization of a novel IL-4 receptor α chain (IL-4Rα) antagonist to inhibit IL-4 signalling, Cellular physiology and biochemistry, vol. 36, no. 3, pp. 831-842, doi: 10.1159/000430259.

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Title Identification and characterization of a novel IL-4 receptor α chain (IL-4Rα) antagonist to inhibit IL-4 signalling
Author(s) Ahmed, Nayyar
Dhanapala, Pathum
Suphioglu, Cenk
Journal name Cellular physiology and biochemistry
Volume number 36
Issue number 3
Start page 831
End page 842
Total pages 12
Publisher Karger
Place of publication Basal, Switzerland
Publication date 2015
ISSN 1421-9778
Keyword(s) Alkaline Phosphatase
Anti-Allergic Agents
Biological Assay
Cell Line
Colorimetry
Gene Expression
HEK293 Cells
Humans
Interleukin-4
Interleukin-4 Receptor alpha Subunit
Peptide Library
Peptides
Protein Binding
Protein Isoforms
Signal Transduction
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Physiology
Allergy
Phage display
IL-4 signalling pathway
IL-4 receptor
IgE
ELISA
HEK-Blue cell line
TUMOR-NECROSIS-FACTOR
PHAGE-DISPLAY
ALLERGIC DISEASES
MONOCLONAL-ANTIBODIES
FRAGMENT LIBRARIES
PEPTIDE LIBRARIES
SOLUBLE RECEPTORS
FOOD ALLERGY
PROTEIN
Summary BACKGROUND/AIMS: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R), consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. METHODS: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. RESULTS: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP). QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. CONCLUSION: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.
Language eng
DOI 10.1159/000430259
Field of Research 060804 Animal Immunology
1116 Medical Physiology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Karger
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080914

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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