دورية أكاديمية
A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models.
العنوان: | A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models. |
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المؤلفون: | Achek A; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Kwon HK; Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06510, USA., Patra MC; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Shah M; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Hong R; Department of Physiology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Lee WH; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Baek WY; Department of Rheumatology, Ajou University School of Medicine, Suwon 16499, Republic of Korea., Choi YS; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Kim GY; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Pham TLH; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Suh CH; Department of Rheumatology, Ajou University School of Medicine, Suwon 16499, Republic of Korea., Kim W; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea., Hahm DH; Department of Physiology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Choi S; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea. Electronic address: sangdunchoi@ajou.ac.kr. |
المصدر: | EBioMedicine [EBioMedicine] 2020 Feb; Vol. 52, pp. 102645. Date of Electronic Publication: 2020 Feb 01. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2014]- |
مواضيع طبية MeSH: | Protein Conformation, beta-Strand*, Membrane Glycoproteins/*chemistry , Peptides/*chemistry , Peptides/*pharmacology , Receptors, Interleukin-1/*chemistry , Toll-Like Receptor 4/*chemistry, Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Autoimmunity ; Cell Line ; Cytokines/metabolism ; Disease Models, Animal ; Immunologic Factors/chemistry ; Immunologic Factors/pharmacology ; Inflammation/drug therapy ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Models, Molecular ; Nitric Oxide/metabolism ; Peptides/metabolism ; Psoriasis/drug therapy ; Psoriasis/immunology ; Psoriasis/metabolism ; Psoriasis/pathology ; Reactive Oxygen Species/metabolism ; Receptors, Interleukin-1/metabolism ; Signal Transduction ; Structure-Activity Relationship ; Toll-Like Receptor 4/metabolism ; Toll-Like Receptors/metabolism |
مستخلص: | Background: TLRs are some of the actively pursued drug-targets in immune disorders. Owing to a recent surge in the cognizance of TLR structural biology and signalling pathways, numerous therapeutic modulators, ranging from low-molecular-weight organic compounds to polypeptides and nucleic acid agents have been developed. Methods: A penetratin-conjugated small peptide (TIP3), derived from the core β-sheet of TIRAP, was evaluated in vitro by monitoring the TLR-mediated cytokine induction and quantifying the protein expression using western blot. The therapeutic potential of TIP3 was further evaluated in TLR-dependent in vivo disease models. Findings: TIP3 blocks the TLR4-mediated cytokine production through both the MyD88- and TRIF-dependent pathways. A similar inhibitory-effect was exhibited for TLR3 but not on other TLRs. A profound therapeutic effect was observed in vivo, where TIP3 successfully alleviated the inflammatory response in mice model of collagen-induced arthritis and ameliorated the disease symptoms in psoriasis and SLE models. Interpretation: Our data suggest that TIP3 may be a potential lead candidate for the development of effective therapeutics against TLR-mediated autoimmune disorders. Funding: This work was supported by the National Research Foundation of Korea (NRF-2019M3A9A8065098, 2019M3D1A1078940 and 2019R1A6A1A11051471). The funders did not have any role in the design of the present study, data collection, data analysis, interpretation, or the writing of the manuscript. Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.) |
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فهرسة مساهمة: | Keywords: Antagonist; Collagen-induced arthritis; Decoy peptide; Psoriasis; Systemic lupus erythematosus; TLR4 |
المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0 (Cytokines) 0 (Immunologic Factors) 0 (Membrane Glycoproteins) 0 (Peptides) 0 (Reactive Oxygen Species) 0 (Receptors, Interleukin-1) 0 (TIRAP protein, human) 0 (Toll-Like Receptor 4) 0 (Toll-Like Receptors) 31C4KY9ESH (Nitric Oxide) |
تواريخ الأحداث: | Date Created: 20200205 Date Completed: 20201008 Latest Revision: 20210110 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6997517 |
DOI: | 10.1016/j.ebiom.2020.102645 |
PMID: | 32014819 |
قاعدة البيانات: | MEDLINE |
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