In Vitro and In Vivo Trypanosomicidal Action of Novel Arylimidamides against Trypanosoma cruzi.

Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono-AIAs against different strains ofT. cruziin vitroandin vivowere analyzed.

A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.

Background: Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS) stimulation. We employed a two-stage framework.

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

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.

Long-term culture of multibacillary leprosy macrophages isolated from skin lesions: a new model to study Mycobacterium leprae-human cell interaction.

Background: Leprosy is characterized by a disease spectrum having two polar clinical forms dependent on the presence or not of cell-mediated immunity. In the tuberculoid forms, granuloma-activated macrophages kill Mycobacterium leprae in conjunction with a Th1 response while, in multibacillary (MB) lesions, M. leprae nonactivated macrophages infiltrate the nerves and internal organs together with a Th2 response.

The proteasome function is required for Mycobacterium leprae-induced apoptosis and cytokine secretion.

Previous studies have demonstrated the importance of the ubiquitin-proteasome pathway in the immune response to bacterial pathogens. To investigate the role of this system in the context of leprosy, Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) were treated with the proteasome inhibitor MG132 to assess the levels of apoptosis and cytokine secretion. The results showed that the inhibition of proteasome activity significantly reduced M.