| Author | Hernandez, Maristela de Oliveira | |
| Author | Fulco, Tatiana de Oliveira | |
| Author | Pinheiro, Roberta Olmo | |
| Author | Pereira, Renata de Meirelles Santos | |
| Author | Redner, Paulo | |
| Author | Sarno, Euzenir Nunes | |
| Author | Lopes, Ulisses Gazos | |
| Author | Sampaio, Elizabeth Pereira | |
| Access date | 2017-01-10T15:22:15Z | |
| Available date | 2017-01-10T15:22:15Z | |
| Document date | 2011 | |
| Citation | HERNANDEZ, Maristela de Oliveira; et al. Thalidomide modulates Mycobacterium leprae-induced NF-κB pathway and lower cytokine response. European Journal of Pharmacology, v.670, p.272–279, 2011. | pt_BR |
| ISSN | 0014-2999 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/16782 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Hanseníase | pt_BR |
| Subject in Portuguese | Talidomida | pt_BR |
| Subject in Portuguese | Mycobacterium leprae | pt_BR |
| Subject in Portuguese | Citocina | pt_BR |
| Title | Thalidomide modulates Mycobacterium leprae-induced NF-κB pathway and lower cytokine response | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.ejphar.2011.08.046 | |
| Abstract | It is widely accepted that tumor necrosis factor alpha (TNF-α) plays a critical role in the development of tissue and nerve damage in leprosy and during the reactional episodes of acute inflammation. Thalidomide (N-α-phthalimidoglutarimide), a drug used to treat leprosy reaction, modulates immune response, inhibits inflammation and NF-κB activity. Here we investigated whether thalidomide inhibits NF-κB activation induced by Mycobacterium leprae, p38 and ERK1/2 MAPK activation. EMSA and supershift assays were performed to investigate NF-κB activation in response to M. leprae and its modulation following in vitro treatment with thalidomide. Luciferase assay was assayed in transfected THP-1 cells to determine NF-κB transcriptional activity. Flow cytometry and immunofluorescence were used to investigate p65 accumulation in the nucleus. Immunoblotting was used to investigate p38 and ERK1/2 phosphorylation. Following activation of PBMC and monocytes with M. leprae, the formation and nuclear localization of NF-κB complexes composed mainly of p65/p50 and p50/p50 dimers was observed. Induction of NF-κB activation and DNA binding activity was inhibited by thalidomide. The drug also reduced M. leprae-induced TNF-α production and inhibited p38 and ERK1/2 activation. Definition of the activation mechanisms in cells stimulated with M. leprae can lead to the development of new therapy applications to modulate NF-κB activation and to control the inflammatory manifestations due to enhanced TNF-α response as observed in leprosy and in leprosy reactions. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil.. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Subject | Thalidomide | pt_BR |
| Subject | NF-κB | pt_BR |
| Subject | TNF-α | pt_BR |
| Subject | M. leprae | pt_BR |
| Subject | Leprosy | pt_BR |
| e-ISSN | 1879-0712 | |
| Embargo date | 2030-01-01 | |
