Clear Search sequence regions


  • A20 (7)
  • amp (2)
  • cells (3)
  • das (1)
  • did (1)
  • family (2)
  • IL 1β (13)
  • impair (1)
  • inflammasomes (2)
  • interleukin 1beta (2)
  • leishmania (2)
  • leishmania donovani (3)
  • leishmaniasis (2)
  • liver (1)
  • macrophage (5)
  • mice (3)
  • NF κB (7)
  • NLR (2)
  • NLRP3 (5)
  • oxygen (4)
  • plasmid (1)
  • pyrin (2)
  • short hairpin rna (1)
  • signal (1)
  • species (4)
  • spleen (1)
  • Tnfaip3 (1)
  • Tumor Necrosis Factor (2)
  • UCP2 (9)
  • Sizes of these terms reflect their relevance to your search.

    In visceral leishmaniasis, we found that the antileishmanial drug Amp B produces a higher level of IL-1β over the infected control. Moreover, administering anti-IL-1β antibody to infected Amp B-treated mice showed significantly less parasite clearance. Investigation revealed that Leishmania inhibits stimuli-induced expression of a multiprotein signaling platform, NLRP3 inflammasome, which in turn inhibits caspase-1 activation mediated maturation of IL-1β from its pro form. Attenuation of NLRP3 and pro-IL-1β in infection was found to result from decreased NF-κB activity. Transfecting infected cells with constitutively active NF-κB plasmid increased NLRP3 and pro-IL-1β expression but did not increase mature IL-1β, suggesting that IL-1β maturation requires a second signal, which was found to be reactive oxygen species (ROS). Decreased NF-κB was attributed to increased expression of A20, a negative regulator of NF-κB signaling. Silencing A20 in infected cells restored NLRP3 and pro-IL-1β expression, but also increased matured IL-1β, implying an NF-κB-independent A20-modulated IL-1β maturation. Macrophage ROS is primarily regulated by mitochondrial uncoupling protein 2 (UCP2), and UCP2-silenced infected cells showed an increased IL-1β level. Short hairpin RNA-mediated knockdown of A20 and UCP2 in infected mice independently documented decreased liver and spleen parasite burden and increased IL-1β production. These results suggest that Leishmania exploits A20 and UCP2 to impair inflammasome activation for disease propagation.-Gupta, A. K., Ghosh, K., Palit, S., Barua, J., Das, P. K., Ukil, A. Leishmania donovani inhibits inflammasome-dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2. © FASEB.

    Citation

    Anand Kumar Gupta, Kuntal Ghosh, Shreyasi Palit, Jayita Barua, Pijush K Das, Anindita Ukil. Leishmania donovani inhibits inflammasome-dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2017 Nov;31(11):5087-5101

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 28765172

    View Full Text