Tumor necrosis factor-alpha and IL-6 up-regulate IFN-gamma receptor gene expression in human monocytic THP-1 cells by transcriptional and post-transcriptional mechanisms
Sanceau, J.; Merlin, G.; Wietzerbin, J.
Journal of Immunology 149(5): 1671-1675
ISSN/ISBN: 0022-1767 PMID: 1387149 Accession: 009680712
IFN-gamma is a potent activator of monocyttic cell functions, including the stimulation of TNF-alpha and the control of IL-6 synthesis. These cytokines might act as autocrine or paracrine factors together with IFN-gamma in inducing biologic responses. In this study, we addressed the question of whether or not TNF-alpha and IL-6 play a role in modulating of IFN-gamma binding. Expression of IFN-gamma surface receptor was measured in the human monocytic THP-1 cells. The capacity of these cells to bind IFN-gamma increased with time after treatment with each cytokine. The number of IFN-gamma-R per cell rose by three- and fourfold after 16 h of treatment with TNF-alpha and IL-6, respectively. Scattchard analysis of binding data showed that neither TNF-alpha nor IL-6 affected the affinity of IFN-gamma for its receptor. The increased surface expression of IFN-gamma-R induced by TNF-alpha and IL-6 correlated wih the rise in IFN-gamma mRNA receptor levels. TNF-alpha-mediated up-regulation of IFN-gamma-R was due to an increase in transcriptional activity of the IFN-gamma-R gene, as shown by run-on experiments. No significant modulation of IFN-gamma-R gene transcription was observed in nuclei from cells treated with IL-6, whose effect appeared to be related to IFN-gamma mRNA receptor stabilization. Taken together, the present results provide, to our knowledge, the first evidence for cytokine-mediated up-regulation of IFN-gamma-R in human monocytic cells. This up-regulattion by TNF-alpha and IL-6, which are both produced by monocytes, occurs through different mechanisms, and may be of physiologic relevance in host defense.