دورية أكاديمية
Antileishmanial drugs activate inflammatory signaling pathways via toll-like receptors (docking approach) from Leishmania amazonensis-infected macrophages.
| العنوان: | Antileishmanial drugs activate inflammatory signaling pathways via toll-like receptors (docking approach) from Leishmania amazonensis-infected macrophages. |
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| المؤلفون: | Valentim-Silva JR; Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ Rondônia), Porto Velho, RO, Brazil; Physical Education Department of Federal University of Rondônia (UNIR), Porto Velho, RO, Brazil; Physical Education Department of University Center UNINORTE, Rio Branco, AC, Brazil., Macedo SRA; Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ Rondônia), Porto Velho, RO, Brazil; União das Escolas Superiores de Rondônia (UNIRON), Porto Velho, RO, Brazil., de Barros NB; Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ Rondônia), Porto Velho, RO, Brazil; Faculdades Integradas Aparício Carvalho (FIMCA), Porto Velho, RO, Brazil., Dos Santos Ferreira A; Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ Rondônia), Porto Velho, RO, Brazil., da Silva JHM; Fundação Oswaldo Cruz (FIOCRUZ Ceará), Eusébio, CE, Brazil., de Figueiredo Nicolete LD; Fundação Oswaldo Cruz (FIOCRUZ Ceará), Eusébio, CE, Brazil; Instituto de Ciências da Saúde da Universidade Internacional da Integração Luso Afro Brasileira (UNILAB), Redenção, CE, Brazil., Nicolete R; Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ Rondônia), Porto Velho, RO, Brazil; Fundação Oswaldo Cruz (FIOCRUZ Ceará), Eusébio, CE, Brazil. Electronic address: rnicolete@gmail.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2020 Aug; Vol. 85, pp. 106640. Date of Electronic Publication: 2020 May 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Leishmania*, Antiprotozoal Agents/*pharmacology , Macrophages/*drug effects , Toll-Like Receptors/*metabolism, Amphotericin B/pharmacology ; Animals ; Cell Line ; Inflammation/immunology ; Leishmaniasis/immunology ; Macrophages/metabolism ; Meglumine Antimoniate/pharmacology ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Docking Simulation ; Pentamidine/pharmacology ; Signal Transduction/drug effects ; Transcription Factor RelA/metabolism |
| مستخلص: | The activation of proinflammatory cellular processes and signals such as those linked to NF-kB in macrophages are involved in the control of infection by Leishmania ssp. However, little is known about the influence of the drugs used in the treatment on the host cellular inflammatory signaling pathways. This study aimed to evaluate the effects of different drugs used in the treatment of leishmaniasis on inflammatory profile related to Toll-like receptors (TLRs) from L. amazonensis-infected macrophages. J774 macrophage-like cells were infected with the promastigote forms (5:1) and 24 hs incubated with Amphotericin B (AmB), Glucantime® (GLU) or Pentamidine (Pent). The following inflammatory pathways were evaluated: NF-κB p65, NF-κB p65 phosphorylated (Ser536), stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) phosphorylated (Thr183/Tyr185), p38 mitogen activated protein kinase (MAPK p38) phosphorylated (Thr180/Tyr182), signal transducer and activator of transcription-3 (Stat3) phosphorylated (Tyr705) and inhibitor kappa B-α (IκB-α) phosphorylated (Ser32). In silico tests were performed to evaluate the molecular affinity between TLRs and antileishmanial drugs. Molecular docking showed that affinities varied significantly among the binders evaluated. The lowest affinity (-8.6 Kcal/Mol) was calculated for AmB in complex with TLR4. Pent showed higher values for TLR1, TLR2 and TLR3, while for TLR4 the affinity value was lower (5.5 Kcal/Mol). The values obtained for GLU were the highest for the set of binders tested. From the infected macrophages, treatments inhibited NF-kB p65 for GLU (65.44%), for Pent (46.43%) and for AmB (54.07%) compared to untreated infected macrophages. The activation of the signaling pathway of NF-kB, SAPK/JNK and IκB-α caused by AmB and Pent may potentiate the microbicidal mechanisms of the infected macrophages. (Copyright © 2020 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antileishmanial drugs; Inflammation; Leishmaniasis; Molecular docking; TLRs |
| المشرفين على المادة: | 0 (Antiprotozoal Agents) 0 (Toll-Like Receptors) 0 (Transcription Factor RelA) 673LC5J4LQ (Pentamidine) 75G4TW236W (Meglumine Antimoniate) 7XU7A7DROE (Amphotericin B) EC 2.7.11.24 (Mitogen-Activated Protein Kinases) |
| تواريخ الأحداث: | Date Created: 20200530 Date Completed: 20210428 Latest Revision: 20210428 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.intimp.2020.106640 |
| PMID: | 32470884 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2020.106640 |