Thalidomide modulates Mycobacterium leprae-induced NF-κB pathway and lower cytokine response.

Autor: Hernandez Mde O; Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil., Fulco Tde O, Pinheiro RO, Pereira Rde M, Redner P, Sarno EN, Lopes UG, Sampaio EP
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2011 Nov 16; Vol. 670 (1), pp. 272-9. Date of Electronic Publication: 2011 Sep 14.
DOI: 10.1016/j.ejphar.2011.08.046
Abstrakt: 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.
(Copyright © 2011 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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