title: Inhibition of Mycobacterium tuberculosis-induced signalling by transforming growth factor-β in human mononuclear phagocytes.
abstract: Tuberculosis (TB) is associated with excessive production and bioactivation of transforming growth factor bets (TGF-β) in situ. Here, modification of expression of components of plasminogen/plasmin pathway in human monocytes (MN) by inhibitors of TGF-β signalling was examined. Smad3 siRNA effectively inhibited TGF-β-induced urokinase plasminogen activator receptor (uPAR). Agents known to interfere with TGF-β signalling, including the Smad inhibitors SIS3 and erythromycin derivatives, and ALK5 receptor inhibitor (SB 431542) in inhibition of uPAR expression in response to Mycobacterium tuberculosis (MTB) were examined. Inhibition by SIS3 only inhibited uPAR mRNA significantly. SIS3 may prove to be an effective adjunct to TB therapy.
authors.affiliation: Case Western Reserve University             Veterans Affairs Medical Center, Cleveland, OH, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Aung
authors.forename: C S
authors.initials: CS
authors.lastname: Hirsch
authors.forename: Z
authors.initials: Z
authors.lastname: Toossi
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology*; D010960:Plasminogen Activators / Q000235:genetics / Q000276:immunology; D015849:Plasminogen Inactivators / Q000235:genetics / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C508504:6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; D001549:Benzamides; D004149:Dioxoles; D007546:Isoquinolines; D015849:Plasminogen Inactivators; D011725:Pyridines; D011758:Pyrroles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D010960:Plasminogen Activators