Modulation of transforming growth factor-beta 1 effects by cytokines.
Journal Title: Immunological Investigations - Year 1993, Vol 22, Issue 5
Abstract
The purpose of the present study was to determine the effects of humanrecombinant transforming growth factor-beta 1 (TGF-beta 1) on the proliferation of normal cell and cancercell lines and to evaluate the mechanism of TGF-beta-induced immunosuppression. Murine H238 fibrosarcomaand human UC-11 glioblastoma cells showed no proliferative change in the presence of TGF-beta, whereasthe growth of human LS174T colon adenocarcinoma cells was significantly enhanced at the lower concentrationsof TGF-beta. In contrast, Mono/Mac-6, a human monocyte cell line, human peripheral blood mononuclear(PBMN) cells, and BALB/c mouse spleen cells were significantly suppressed by 2.5 to 250 ng/ml of TGF-beta.In order to investigate the mode of action, TGF-beta and other cytokines were added 0, 1, and 2 daysafter initiation of the culture. Mono/Mac-6 cells showed that 2 days are needed for TGF-beta-inducedsuppression. Simultaneous addition of TGF-beta and tumor necrosis-alpha (TNF-alpha; 600 units/ml) toMono/Mac-6 cells resulted in nearly complete suppression by day 3. IL-2, and to a lesser extent IL-4,was able to counteract the suppressive effects of TGF-beta on mitogen-stimulated spleen cells. However,our results indicate that IL-2 is not as effective in restoring responsiveness once T cell activationis well underway. IL-1 and interferon-gamma had no effects on TGF-beta-mediated immunosuppression. SinceTGF-beta depressed normal cell growth and since IL-2 could effectively counteract the suppression, weassayed for IL-2 production. When normal spleen cells were treated with 2.5 ng of TGF-beta/ml, a 3.4-folddecrease in IL-2 production was observed. This is a potential mechanism for TGF-beta-mediated immunosuppression.
Authors and Affiliations
J R Uhm, J D Kettering, D S Gridley
Keywords
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Modulation of transforming growth factor-beta 1 effects by cytokines.
The purpose of the present study was to determine the effects of humanrecombinant transforming growth factor-beta 1 (TGF-beta 1) on the proliferation of normal cell and cancercell lines and to evaluate the mechanism of T...