Mycobacterium leprae induces NF-kappaB-dependent transcription repression in human Schwann cells.
Mycobacterium leprae, the causative agent of leprosy, invades peripheral nerve Schwann cells, resulting in deformities associated with this disease. NF-kappaB is an important transcription factor involved in the regulation of host immune antimicrobial responses. We aimed in this work to investigate NF-kappaB signaling pathways in the human ST88-14 Schwannoma cell line infected with M. leprae. Gel shift and supershift assays indicate that two NF-kappaB dimers, p65/p50 and p50/p50, translocate to the nucleus in Schwann cells treated with lethally irradiated M. leprae. Consistent with p65/p50 and p50/p50 activation, we observed IkappaB-alpha degradation and reduction of p105 levels. The nuclear translocation of p50/p50 complex due to M. leprae treatment correlated with repression of NF-kappaB-driven transcription induced by TNF-alpha. Moreover, thalidomide inhibited p50 homodimer nuclear translocation induced by M. leprae and consequently rescues Schwann cells from NF-kappaB-dependent transcriptional repression. Here, we report for the first time that M. leprae induces NF-kappaB activation in Schwann cells and thalidomide is able to modulate this activation.
Pereira
Renata M S
RM
Laboratório de Parasitologia Molecular, Instituto de Biofísica Carlos Chagas Filho, CCS, UFRJ, Rio de Janeiro, Brazil.
Calegari-Silva
Teresa Cristina
TC
Hernandez
Maristela O
MO
Saliba
Alessandra M
AM
Redner
Paulo
P
Pessolani
Maria Cristina V
MC
Sarno
Euzenir N
EN
Sampaio
Elizabeth P
EP
Lopes
Ulisses G
UG
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009166:Mycobacterium leprae / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D013792:Thalidomide / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide