actinomycetemcomitans killing neutrophils [50–52] in test for opsonizing potential. Thus, studies of the antibody characteristics as they relate to subclass distribution and targeted functions, comparing the response to pathogens and commensals must be conducted to understand more fully the in vivo ramifications of the host discrimination of these bacteria coupled with the ability of the antibodies to modulate the oral microbial burden in health and disease.

None of the authors have any financial conflicts to disclose. “
“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 R788 supplier 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. A prominent role for TGF-β in macrophage deactivation and suppression of T cell responses to Mycobacterium tuberculosis (MTB) is well established (Reviewed in [1]). Excessive PD0325901 molecular weight TGF-β activity is a feature of active pulmonary TB [2], and human mononuclear phagocytes that are infected or exposed to MTB or its components in vitro. Importantly, lung lavage from patients with active TB contain Atazanavir bioactive TGF-β [3], implicating that conditions for TGF-β signalling are present in situ. In a murine model of M. bovis pulmonary infection, administration of latency-associated peptide of TGF-β, modified TGF-β bioactivity

in situ and both decreased BCG growth in the lung and enhanced antigen-specific T cell responses [4]. In vitro, MTB stimulation of human mononuclear phagocytes also leads to production of bioactive TGF-β [5]. Collectively, these data implicate that both production of TGF-β itself and the molecular context necessary for its bioactivation are present at sites of MTB infection. Recently, several inhibitors of TGF-β bioactivity have been developed. Whether TGF-β signalling can be aborted by any of these agents during MTB infection is currently unknown. Inhibitors of TGF-β signalling, however, may have a role as adjuncts to antituberculosis therapy. Binding of bioactive TGF-β to homodimeric type II TGF-β receptor leads to recruitment and activation of homodimeric type 1 receptor (also known as activin-like receptor kinases [ALK]. This then leads to phosphorylation of Smads2 and 3, which in turn form heterodimers with Smad4, and then the complex translocates into the nucleus, ultimately leading to TGF-β bioactivity [6].