Induction of transforming growth factor β1 by purified protein derivative of Mycobacterium tuberculosis

We examined the ability of purified protein derivative (PPD) of Mycobacterium tuberculosis to induce transforming growth factor β1 (TGF- β1), a potent immunosuppressive and macrophage-deactivating molecule, in blood monocytes from healthy individuals. TBF-β1 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-β1 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-β1 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-β1 mRNA. Decay studies suggested a transcriptional rather than a posttranscriptional effect of PPD on TGF-β1 gene expression.