Mycobacterium leprae, the causative agent of leprosy, invades peripheral nerve Schwarm cells, resulting in deformities associated with this disease. NF-kappa B is an important transcription factor involved in the regulation of host immune antimicrobial responses. We aimed in this work to investigate NF-kappa B signaling pathways in the human ST88-14 Schwannoma cell line infected with M. leprae. Gel shift and supershift assays indicate that two NF-kappa B dimers, p65/p50 and p50/p50, translocate to the nucleus in Schwarm cells treated with lethally irradiated M. leprae. Consistent with p65/p50 and p50/p50 activation, we observed I kappa B-alpha degradation and reduction of p105 levels. The nuclear translocation of p50/p50 complex due to M. leprae treatment correlated with repression of NF-kappa B-driven transcription induced by TNF-alpha. Moreover, thalidomide inhibited p50 homodimer nuclear translocation induced by M. leprae and consequently rescues Schwann cells from NF-kappa B-dependent transcriptional repression. Here, we report for the first time that M. leprae induces NF-kappa B activation in Schwarm cells and thalidomide is able to modulate this activation. (c) 2005 Elsevier Inc. All rights reserved.