دورية أكاديمية
Mechanism of Anti-Inflammatory Activity of TLR4-Interacting SPA4 Peptide.
العنوان: | Mechanism of Anti-Inflammatory Activity of TLR4-Interacting SPA4 Peptide. |
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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.) |
References: | J Leukoc Biol. 2015 Dec;98(6):1037-48. (PMID: 26254306) Oncoimmunology. 2012 Dec 1;1(9):1495-1506. (PMID: 23264896) Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W665-7. (PMID: 15215472) RSC Adv. 2015;5(35):27431-27438. (PMID: 25870755) J Immunol Methods. 1983 Dec 16;65(1-2):55-63. (PMID: 6606682) Biochem Biophys Res Commun. 2017 Mar 25;485(1):107-112. (PMID: 28188794) Annu Rev Pathol. 2011;6:147-63. (PMID: 20936936) Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W310-4. (PMID: 16845016) J Biol Chem. 2003 Oct 31;278(44):43254-60. (PMID: 12913002) Int J Mol Med. 2019 May;43(5):2064-2074. (PMID: 30864740) Curr Opin Immunol. 2000 Feb;12(1):20-6. (PMID: 10679411) J Allergy Clin Immunol. 2001 Aug;108(2):157-66. (PMID: 11496229) Am J Ind Med. 2001 Jun;39(6):616-28. (PMID: 11385646) J Pharmacol Exp Ther. 2011 Mar;336(3):672-81. (PMID: 21159752) Am J Respir Crit Care Med. 1995 Aug;152(2):603-8. (PMID: 7633714) J Immunol. 2015 Feb 1;194(3):855-60. (PMID: 25596299) Med Sci Monit. 2019 Mar 28;25:2278-2288. (PMID: 30921298) Transl Res. 2016 Jan;167(1):183-91. (PMID: 26003524) Toxicol Pathol. 2015 Dec;43(8):1074-92. (PMID: 26296628) Bioinformatics. 2008 Sep 15;24(18):2101-2. (PMID: 18662927) Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1641-6. (PMID: 8970348) Immunobiology. 2017 Feb;222(2):111-118. (PMID: 27793398) Cell Immunol. 2011;268(2):87-96. (PMID: 21439559) Biochemistry. 2016 Jul 5;55(26):3692-701. (PMID: 27324153) Ther Adv Respir Dis. 2015 Aug;9(4):173-87. (PMID: 26002528) Nature. 2009 Apr 30;458(7242):1191-5. (PMID: 19252480) Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L743-50. (PMID: 11880300) Nucleic Acids Res. 2016 Jan 4;44(D1):D1087-93. (PMID: 26602694) BMC Bioinformatics. 2007 Feb 27;8:65. (PMID: 17324296) J Biol Chem. 2012 Apr 27;287(18):15034-43. (PMID: 22418431) BMC Pulm Med. 2020 Jun 23;20(1):179. (PMID: 32576172) Innate Immun. 2013 Dec;19(6):596-610. (PMID: 23475791) Biol Direct. 2016 Oct 21;11(1):55. (PMID: 27769290) Pediatr Res. 1996 Jun;39(6):938-46. (PMID: 8725252) |
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 |
تدمد: | 2573-7732 |
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DOI: | 10.4049/immunohorizons.2100067 |