دورية أكاديمية
أعرض في EDS

Mechanism of Anti-Inflammatory Activity of TLR4-Interacting SPA4 Peptide.

التفاصيل البيبلوغرافية
العنوان: Mechanism of Anti-Inflammatory Activity of TLR4-Interacting SPA4 Peptide.
المؤلفون: Awasthi S; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Shanjana-Awasthi@ouhsc.edu., Kumar G; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Ramani V; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Awasthi V; Research Imaging Facility, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK; and., Rodgers KK; Department of Biochemistry and Molecular Biology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Xie J; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Beierle J; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Kyere-Davies G; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Singh B; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Rahman N; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Chowdhury AA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Chataut N; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
المصدر: ImmunoHorizons [Immunohorizons] 2021 Aug 24; Vol. 5 (8), pp. 659-674. Date of Electronic Publication: 2021 Aug 24.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association of Immunologists, Inc Country of Publication: United States NLM ID: 101708159 Publication Model: Electronic Cited Medium: Internet ISSN: 2573-7732 (Electronic) Linking ISSN: 25737732 NLM ISO Abbreviation: Immunohorizons Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Rockville, Maryland : American Association of Immunologists, Inc., [2017]-
مواضيع طبية MeSH: Anti-Inflammatory Agents/*pharmacology , Inflammation/*prevention & control , Peptide Fragments/*pharmacology , Pulmonary Surfactant-Associated Protein A/*metabolism , Toll-Like Receptor 4/*metabolism, Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents/metabolism ; Cell Line ; Cell Survival/drug effects ; Cell Survival/genetics ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/metabolism ; Female ; Gene Expression Regulation/drug effects ; HEK293 Cells ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; Lipopolysaccharides/pharmacology ; Mice, Inbred C57BL ; Mutation ; Peptide Fragments/genetics ; Peptide Fragments/metabolism ; Protein Binding ; Pulmonary Surfactant-Associated Protein A/chemistry ; Pulmonary Surfactant-Associated Protein A/genetics ; Mice
مستخلص: The TLR4-interacting SPA4 peptide suppresses inflammation. We assessed the structural and physicochemical properties and binding of SPA4 peptide to TLR4-MD2. We also studied the changes at the whole transcriptome level, cell morphology, viability, secreted cytokines and chemokines, and cell influx in cell systems and mouse models challenged with LPS and treated with SPA4 peptide. Our results demonstrated that the SPA4 peptide did not alter the cell viability and size and only moderately affected the transcriptome of the cells. Computational docking and rendering suggested that the SPA4 peptide intercalates with LPS-induced TLR4-MD2 complex. Results with alanine mutations of D-2 amino acid and NYTXXXRG-12-19 motif of SPA4 peptide suggested their role in binding to TLR4 and in reducing the cytokine response against LPS stimulus. Furthermore, therapeutically administered SPA4 peptide significantly suppressed the secreted levels of cytokines and chemokines in cells and bronchoalveolar lavage fluids of LPS-challenged mice. The results suggest that the SPA4 peptide intercalates with LPS-induced TLR4 complex and signaling for the suppression of inflammation.
(Copyright © 2021 The Authors.)
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معلومات مُعتمدة: P20 GM103648 United States GM NIGMS NIH HHS; R01 HL136325 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (Anti-Inflammatory Agents)
0 (Cytokines)
0 (Lipopolysaccharides)
0 (Peptide Fragments)
0 (Pulmonary Surfactant-Associated Protein A)
0 (Toll-Like Receptor 4)
تواريخ الأحداث: Date Created: 20210825 Date Completed: 20220128 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8673433
DOI: 10.4049/immunohorizons.2100067
PMID: 34429343
قاعدة البيانات: MEDLINE
الوصف
تدمد:2573-7732
DOI:10.4049/immunohorizons.2100067