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

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Abstract
Transforming growth factor (TGF)‐β is a multifunctional cytokine, which in mammals exists in three isoforms (TGF‐β1, 2 and 3). It is synthesized by a variety of cells including macrophages, and exerts potent immunoregulatory effects such as the inhibition of Th1 development and the suppression or reversal of IFN‐γ‐induced macrophage activation. In this study we analyzed the effect of IFN‐γ on the production of TGF‐β1 by thioglycolate‐elicited mouse peritoneal macrophages under serum‐free conditions. Untreated macrophages released TGF‐β1 in its latent form, which became detectable in a capture ELISA specific for active TGF‐β1 after acid activation of the culture supernatants. Treatment with IFN‐γ reduced the amount of latent TGF‐β1 in the culture supernatants in a dose‐dependent fashion. The effect of IFN‐γ was confirmed by a newly developed Western blot system for the detection of mouse TGF‐β1 protein. IFN‐γ only weakly (16 – 24 %) reduced the levels TGF‐β1 mRNA at early and late time points of stimulation, and no evidence was obtained that IFN‐γ suppresses the secretion of latent TGF‐β1. Thus, inhibition of TGF‐β1 production by IFN‐γ is most likely due to decreased synthesis and/or stability of the TGF‐β1 protein, and might be important for the generation of fully activated macrophages and a Th1 response.

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