INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 BY PURIFIED PROTEIN DERIVATIVE OF MYCOBACTERIUM-TUBERCULOSIS

We examined the ability of purified protein derivative (PPD) of Mycoba cterium tuberculosis to induce transforming growth factor beta 1 (TGF- beta 1), a potent immunosuppressive and macrophage-deactivating molecu le, in blood monocytes from healthy individuals. TBF-beta 1 activity i n PPD-induced monocyte supernatants was identified by Western immunobl ot analysis and was not inhibited by polymyxin B, an inhibitor of bact erial lipopolysaccharide (LPS). Furthermore, PPD at equivalent amounts in weight to LPS was as potent in stimulation of monocyte production of TGF-beta 1 at 24 h of culture, as quantified by enzyme-linked immun osorbent assay. The inducing effect of PPD, in contrast to that of LPS , was sustained at later time points of culture (72 h). PPD enhanced t he constitutive expression of TGF-beta 1 steady-state mRNA in monocyte s at 24 and 48 h of culture. In contrast, neither mycobacterial heat s hock protein (64-kDa protein of M. bovis) nor LPS induced TGF-beta 1 m RNA. Decay studies suggested a transcriptional rather than a posttrans criptional effect of PPD on TGF-beta 1 gene expression.