TGF-beta regulates production of growth factors and TGF-beta by human peripheral blood monocytes.
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.
McCartney-Francis
N
N
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Mizel
D
D
Wong
H
H
Wahl
L
L
Wahl
S
S
D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006207:Half-Life; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015342:DNA Probes; D006133:Growth Substances; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D012313:RNA; D003513:Cycloheximide