TGF-β Regulates Production of Growth Factors and TGF-β by Human Peripheral Blood Monocytes

Abstract

Transforming growth factor beta 1 (TGF-β1) and its closely related homologue, TGF-β2, rapidly induce growth factor gene expression by freshly isolated human peripheral blood monocytes. Within 3 h of exposure to TGF-β, mRNA species specific for interleukin-1 (IL-1β), tumor necrosis factor-α (TNF-α), 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-β1, but also TGF-β2 mRNA are expressed constitutively in unstimulated monocytes. However, in response to exogenous TGF-β (βl or β2), only TGF-β1 gene expression is upregulated, and the expression of TGF-β2 mRNA is unchanged. This selective autoinduction of TGF-β1 appears to be controlled at both transcriptional and post-transcriptional levels. These paracrine and autocrine activities of TGF-β suggest potential mechanisms through which an inflammatory response can be initiated and amplified. In addition, the TGF-β enhancement of growth factor generation may promote fibrosis and angiogenesis relevant to physiological tissue repair as well as pathological fibrotic sequelae.