Inhibition of Mycobacterium tuberculosis-Induced Signalling by Transforming Growth Factor-β in Human Mononuclear Phagocytes

We found that an inhibitor of plasmin, reduced Mycobacterium tuberculosis -induced bioactive transforming growth factor bets production in monocytes, implicating involvement of the

M. Wu

2011

Scholarcy highlights

  • A prominent role for transforming growth factor bets in macrophage deactivation and suppression of T cell responses to Mycobacterium tuberculosis is well established
  • To investigate the role of TGF-b signalling in primary human MN, we used siRNA to Smad3 and assessed for genes in the plasmin ⁄ plasminogen pathway of TGF-b bioactivation
  • Whereas uPAR expression was induced about 4- to 30-fold by TGF-b, that of PA1 and uPA mRNA were induced very little
  • UPAR mRNA levels were significantly elevated in TB involved as compared to TB uninvolved lung lavage from patients with smear negative pulmonary TB
  • These data are supportive of use of TGF-b signalling inhibitors as adjuncts to antituberculosis therapy
  • None of the macrolides used were effective in inhibition of TGF-b signalling in induction of uPAR mRNA in human MN
  • 9 Yu C, Azuma A, Li Y et al EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts

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