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A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice

OBJECTIVE: To discover a novel peptoid antagonist that targets the interleukin‐15 (IL‐15) receptor and to evaluate its therapeutic efficacy in the treatment of inflammation and arthritis. METHODS: A new compound (IFRA3, interleukin‐15 receptor antagonist 3) was discovered using a unique on‐bead two‐...

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Autores principales: Cho, Kwang Bog, Shukla, Satya Prakash, Kannan, Maheshkumar, Zhang, Haowen, Amina, Sundus Jabeen, Zhou, Shuang, Chen, Yanping, Molligan, Jeremiah F, Taneja, Veena, Mohan, Chandra, Udugamasooriya, D Gomika, Guo, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686008/
https://www.ncbi.nlm.nih.gov/pubmed/36439637
http://dx.doi.org/10.1002/cti2.1432
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author Cho, Kwang Bog
Shukla, Satya Prakash
Kannan, Maheshkumar
Zhang, Haowen
Amina, Sundus Jabeen
Zhou, Shuang
Chen, Yanping
Molligan, Jeremiah F
Taneja, Veena
Mohan, Chandra
Udugamasooriya, D Gomika
Guo, Bin
author_facet Cho, Kwang Bog
Shukla, Satya Prakash
Kannan, Maheshkumar
Zhang, Haowen
Amina, Sundus Jabeen
Zhou, Shuang
Chen, Yanping
Molligan, Jeremiah F
Taneja, Veena
Mohan, Chandra
Udugamasooriya, D Gomika
Guo, Bin
author_sort Cho, Kwang Bog
collection PubMed
description OBJECTIVE: To discover a novel peptoid antagonist that targets the interleukin‐15 (IL‐15) receptor and to evaluate its therapeutic efficacy in the treatment of inflammation and arthritis. METHODS: A new compound (IFRA3, interleukin‐15 receptor antagonist 3) was discovered using a unique on‐bead two‐colour combinatorial cell screening of a peptoid library. The interaction of IFRA3 with IL‐15 receptor was assessed by in vitro pull‐down and thermal shift assays. The efficacy of IFRA3 in treating inflammation and arthritis was evaluated in mouse models. RESULTS: IFRA3Q1 (a tetrameric derivative of IFRA3) inhibited the activity of IL‐15 and suppressed CTLL‐2 cell proliferation (which depends on IL‐15 activity). IFRA3Q1 exhibited strong in vivo anti‐inflammatory activity in carrageenan‐induced inflammation in mice. Furthermore, IFRA3Q1 inhibited collagen‐induced arthritis in DBA/1J mice. CONCLUSION: By binding to and inhibiting the function of IL‐15 receptor, IFRA3Q1 exhibited significant anti‐arthritis activity. Our findings suggest that IFRA3Q1 represents a new paradigm for arthritis therapy by targeting IL‐15 signalling.
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spelling pubmed-96860082022-11-25 A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice Cho, Kwang Bog Shukla, Satya Prakash Kannan, Maheshkumar Zhang, Haowen Amina, Sundus Jabeen Zhou, Shuang Chen, Yanping Molligan, Jeremiah F Taneja, Veena Mohan, Chandra Udugamasooriya, D Gomika Guo, Bin Clin Transl Immunology Original Articles OBJECTIVE: To discover a novel peptoid antagonist that targets the interleukin‐15 (IL‐15) receptor and to evaluate its therapeutic efficacy in the treatment of inflammation and arthritis. METHODS: A new compound (IFRA3, interleukin‐15 receptor antagonist 3) was discovered using a unique on‐bead two‐colour combinatorial cell screening of a peptoid library. The interaction of IFRA3 with IL‐15 receptor was assessed by in vitro pull‐down and thermal shift assays. The efficacy of IFRA3 in treating inflammation and arthritis was evaluated in mouse models. RESULTS: IFRA3Q1 (a tetrameric derivative of IFRA3) inhibited the activity of IL‐15 and suppressed CTLL‐2 cell proliferation (which depends on IL‐15 activity). IFRA3Q1 exhibited strong in vivo anti‐inflammatory activity in carrageenan‐induced inflammation in mice. Furthermore, IFRA3Q1 inhibited collagen‐induced arthritis in DBA/1J mice. CONCLUSION: By binding to and inhibiting the function of IL‐15 receptor, IFRA3Q1 exhibited significant anti‐arthritis activity. Our findings suggest that IFRA3Q1 represents a new paradigm for arthritis therapy by targeting IL‐15 signalling. John Wiley and Sons Inc. 2022-11-24 /pmc/articles/PMC9686008/ /pubmed/36439637 http://dx.doi.org/10.1002/cti2.1432 Text en © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd, on behalf of Australian and New Zealand Society for Immunology, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Cho, Kwang Bog
Shukla, Satya Prakash
Kannan, Maheshkumar
Zhang, Haowen
Amina, Sundus Jabeen
Zhou, Shuang
Chen, Yanping
Molligan, Jeremiah F
Taneja, Veena
Mohan, Chandra
Udugamasooriya, D Gomika
Guo, Bin
A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title_full A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title_fullStr A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title_full_unstemmed A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title_short A peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
title_sort peptoid interleukin‐15 receptor antagonist suppresses inflammation and arthritis in mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686008/
https://www.ncbi.nlm.nih.gov/pubmed/36439637
http://dx.doi.org/10.1002/cti2.1432
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