دورية أكاديمية
Role of an indole-thiazolidiene PPAR pan ligand on actions elicited by G-protein coupled receptor activated neutrophils.
| العنوان: | Role of an indole-thiazolidiene PPAR pan ligand on actions elicited by G-protein coupled receptor activated neutrophils. |
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| المؤلفون: | Santin JR; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Machado ID; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Drewes CC; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., de Vinci Kanda Kupa L; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Soares RM; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Cavalcanti DM; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., da Rocha Pitta I; Department of Chemistry, Federal University of Pernambuco, Pernambuco, Recife, Brazil., Farsky SHP; Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: sfarsky@usp.br. |
| المصدر: | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Sep; Vol. 105, pp. 947-955. Date of Electronic Publication: 2018 Jun 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982- |
| مواضيع طبية MeSH: | Cyclooxygenase Inhibitors/*pharmacology , Indoles/*pharmacology , Neutrophils/*drug effects , Neutrophils/*metabolism , Peroxisome Proliferator-Activated Receptors/*metabolism , Receptors, G-Protein-Coupled/*metabolism , Thiazolidinediones/*pharmacology, Animals ; Dose-Response Relationship, Drug ; Ligands ; Male ; Peroxisome Proliferator-Activated Receptors/agonists ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled/agonists ; Thiazolidines/pharmacology |
| مستخلص: | Neutrophils are the first line of defence during inflammatory processes; nevertheless, exacerbated influx and actions of neutrophils in terms of uncontrolled inflammation are harmful to the host. Hence, neutrophil activity is the target of drugs seeking to address undesired inflammation. Here, we investigated the mechanisms of action of a ligand of the three isoforms of peroxisome proliferator-activated receptors (PPAR; (5Z)-5-[(5-bromo-1H-indole-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione), dubbed LYSO-7, on neutrophils activated by N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), an agonist of G-protein coupled receptors (GPCRs) that binds to membrane-formylated peptide and activates intracellular inflammation pathways. Neutrophils were collected from the peritoneal cavity of male Wistar rats four hours after oyster glycogen injection. Afterwards, the neutrophils were incubated with saline or LYSO-7 (1 or 10 μM, 30 min), washed and stimulated with fMLP (10 -7 μM, 1 h). LYSO-7 treatment inhibited gene and protein expression of adhesion molecules, CD62 L and CD18, abolished adhesion of neutrophils to endothelial cells, impaired chemotaxis, blocked the enhancement of intracellular calcium levels, induced the expression of PPARγ as well as PPARβδ and reduced nuclear translocation of nuclear factor κB (NF-κB). Moreover, topical application of LYSO-7 (10 mM) prior to local application of fMLP (10 -7 μM) diminished the in vivo leukocyte-endothelial interactions in the mesentery microcirculation of rats. Together, our data highlight the effectiveness of anti-inflammatory actions of LYSO-7 on neutrophils activated by GPCRs, depending, at least in part, on impaired of NF-κB activation and induction of PPAR expression. (Copyright © 2018 Elsevier Masson SAS. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Chemotaxis; Inflammation; NF-κB; Neutrophil-endothelial interactions; fMLP |
| المشرفين على المادة: | 0 (5-((5-bromo-1H-indol-3-yl)methylene)-3-(4-chlorobenzyl)thiazolidine-2,4-dione) 0 (Cyclooxygenase Inhibitors) 0 (Indoles) 0 (Ligands) 0 (Peroxisome Proliferator-Activated Receptors) 0 (Receptors, G-Protein-Coupled) 0 (Thiazolidinediones) 0 (Thiazolidines) |
| تواريخ الأحداث: | Date Created: 20180720 Date Completed: 20181102 Latest Revision: 20181102 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.biopha.2018.06.056 |
| PMID: | 30021389 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1950-6007 |
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| DOI: | 10.1016/j.biopha.2018.06.056 |