Transforming growth factor-β1 inhibits activation of macrophage cell line RAW 264.7 for cell killing

Abstract

SUMMARY Transforming growth factor β-1 (TGF-β) is a multi-potent immunoregulatory peptide that has effects on numerous cell types. Here we report that human TGF-β inhibits the activation of the macrophagc cell line RAW 264.7 for killing of the L1210 tumour cell line. RAW 264.7 cells, like normal macrophages, require sequential interaction with priming and triggering stimuli for full activation of cytolytic activity. TGF-β inhibits this cytotoxicity in a dose-dependent manner at both the priming and the triggering stage. Addition of as little as 1 ng/ml TGF-β when added with either the priming signal, recombinant interferon-gamma (IFN-γ), or the triggering signal, bacterial lipopolysaccharide (LPS), completely abrogated tumouricidal activity. Incubation with TGF-β also inhibited the morphological changes normally observed in activated RAW 264.7 cells. However. TGF-β was unable to inhibit the cytotoxic activity of RAW 264.7 cells against the target cell line WEHI 164, which is sensitive to tumour necrosis factor. In contrast to the effects on cytotoxic activity, the cytostatic activity of activated RAW 264.7 cells was not inhibited by TGF-β at doses of up to 5 ng/ml. In addition, pretreatment of the LI210 target cells with TGF-β made them refractory to both the cytostatic and cytotoxic effects of RAW 264.7 cells. These data suggest that TGF-β may be an important mediator in the regulation of macrophage tumouricidal activity.