TGF-beta regulates production of growth factors and TGF-beta by human peripheral blood monocytes

Abstract

Transforming growth factor beta 1 (TGF-beta 1) and its closely related homologue, TGF-beta 2, rapidly induce growth factor gene expression by freshly isolated human peripheral blood monocytes. Within 3 h of exposure to TGF-beta, mRNA species specific for interleukin-1 (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were observed. By 14-18 h, cytokine bioactivity and protein were detected in the culture supernatants. Furthermore, not only TGF-beta 1, but also TGF-beta 2 mRNA are expressed constitutively in unstimulated monocytes. However, in response to exogenous TGF-beta (beta 1 or beta 2), only TGF-beta 1 gene expression is upregulated, and the expression of TGF-beta 2 mRNA is unchanged. This selective autoinduction of TGF-beta 1 appears to be controlled at both transcriptional and post-transcriptional levels. These paracrine and autocrine activities of TGF-beta suggest potential mechanisms through which an inflammatory response can be initiated and amplified. In addition, the TGF-beta enhancement of growth factor generation may promote fibrosis and angiogenesis relevant to physiological tissue repair as well as pathological fibrotic sequelae.