Induction of transforming growth factor beta 1 by purified protein derivative of Mycobacterium tuberculosis

Abstract

We examined the ability of purified protein derivative (PPD) of Mycobacterium tuberculosis to induce transforming growth factor ␤1 (TGF-␤1), a potent immunosuppressive and macrophage-deactivating molecule, in blood monocytes from healthy individuals. TBF-␤1 activity in PPD-induced monocyte supernatants was identified by Western immunoblot analysis and was not inhibited by polymyxin B, an inhibitor of bacterial lipopolysaccharide (LPS). Furthermore, PPD at equivalent amounts in weight to LPS was as potent in stimulation of monocyte production of TGF-␤1 at 24 h of culture, as quantified by enzyme-linked immunosorbent assay. The inducing effect of PPD, in contrast to that of LPS, was sustained at later time points of culture (72 h). PPD enhanced the constitutive expression of TGF-␤1 steady-state mRNA in monocytes at 24 and 48 h of culture. In contrast, neither mycobacterial heat shock protein (64-kDa protein of M. bovis) nor LPS induced TGF-␤1 mRNA. Decay studies suggested a transcriptional rather than a posttranscriptional effect of PPD on TGF-␤1 gene expression.

Expression of Transforming Growth Factor‐β Isoforms and Their Receptors in Lepromatous and Tuberculoid Leprosy

“…Some studies in vitro have shown that mycobacteria and some of its components are efficient inducers of TGF-b production by macrophages [19,20], and that the low Th1 cytokine expression present in LL could also induce high expression of TGF-b [21]. Furthermore, high TGF-b1 expression in LL has been observed [22,23].…”

Induction and Activation of Latent Transforming Growth Factor-β1 Are Carried out by Two Distinct Domains of Pregnancy-specific Glycoprotein 1 (PSG1)

“…To date, few factors have been described that induce the secretion of TGF-␤ 1 in distinct cell populations. In addition to PSGs, the induction of TGF-␤ 1 has been described in macrophages treated with apoptotic lymphocytes (16,17), Mycobacterium tuberculosis lipoarabinomannan (18), and lipopolysaccharide (19). We re-examined the induction of TGF-␤ 1 by PSG1 and found that the N-terminal domain alone is sufficient for macrophage TGF-␤ 1 production.…”

IFN-γ inhibits the production of latent transforming growth factor-β1 by mouse inflammatory macrophages

“…3A). Interestingly, in human monocytes LPS alone was shown to reduce the expression of TGF-g 1 mRNA despite stimulating the release of TGF-g protein [24,25,28]. The almost unaltered TGF-g 1 mRNA expression in the macrophages strongly supports the idea that IFN-+ primarily acts on the protein level, either by inhibiting the secretion of latent TGF-g 1, or by decreasing the synthesis and/or stability of the TGF-g 1 protein.…”

“…This contrasts with previous data by Nunes et al [7] on mouse macrophages, where LPS (100 ng/ml) caused a weak increase of total TGF-g (as determined in a bioassay), and with a series of studies on human blood monocytes, which revealed a striking increase of total TGF-g or TGFg 1 after stimulation with 10 ? g/ml LPS [23][24][25]. When we stimulated the macrophages with a combination of IFN-+ (20 ng/ml) and LPS (0.002-200 ng/ml), the amount of latent TGF-g 1 in the SN was further reduced compared to IFN-+ alone, indicating an additive effect of IFN-+ and LPS (Fig.…”