Interferon gamma and interleukin 2 synergize to induce selective monokine expression in murine peritoneal macrophages (original) (raw)
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2001
We have examined the effects of interleukin 2 (IL-2) treatment either alone or in combination with interferon (IFN) y or ,8 on the expression of several activation associated genes (e.g. tumor necrosis factor (Y (TNFa), IFN-inducible lo-kDa protein (IP-10)) in murine peritoneal macrophages. IL-2 alone did not induce the expression of either gene while 1FN-y or IFNj3 had a modest inductive effect on IP-10 but no effect on TNFa! expression. When either form of IFN was used in combination with IL-2 there was a marked synergistic induction of both mRNAs. IFNy and IL-2 were maximally effective when both agents were added simultaneously, and induced mRNA expression declined over a 24-h period in cells pretreated with IFNy prior to addition of IL-2. Expression of both genes following combination lymphokine treatment was mediated by increased transcriptional activity. The responses to all three lymphokines were dose dependent; the concentration requirement for IL-2 indicated interaction wit...
IL-2 induces expression and secretion of IFN-γ in murine peritoneal macrophages
Journal of Leukocyte Biology, 2005
We investigated the effect of interleukin (IL)-2, a T cell growth factor capable of activating certain macrophage functions, on interferon (IFN)-γ expression in resting mouse peritoneal macrophages (PM). IL-2 addition to PM from different mouse strains up-modulated IFN-γ mRNA and protein secretion. It is notable that endogenous type I and II IFNs did not play any role in the IL-2-mediated effect, as comparable levels of secreted IFN-γ were observed upon IL-2 stimulation of PM from deficient mice. In contrast, endogenous IFN-γ was requested for the IL-12-induced IFN-γ production. It is interesting that blocking of each component of the IL-2 receptor (IL-2R) by neutralizing antibodies almost completely abolished IL-2-induced IFN-γ production, suggesting that all IL-2R chains contribute to the PM biological response to IL-2. The simultaneous treatment of PM with IL-2 and IL-12 resulted in a higher IFN-γ secretion with respect to that obtained upon treatment with IL-2 or IL-12 alone. It...
Blood
The interleukin-2 receptor gamma chain (IL-2R gamma) gene codes for a subunit of the IL-2R and is expressed in human lymphoid cells. The present study was undertaken to determine whether human monocytes expressed the IL-2R gamma gene constitutively or after activation by IL-2 or interferon gamma (IFN gamma). Fresh human monocytes constitutively expressed low but significant levels of IL-2R gamma mRNA, and nuclear run-on experiments showed that IL-2R gamma gene was transcriptionally active. Stimulation with IL-2 or IFN gamma induced a major increase of IL-2R gamma mRNA in a time- and a dose-dependent manner. However, neither cytokine increased the transcriptional activity of the gene. The enhancement of IL-2R gamma mRNA expression by either IL-2 or IFN gamma was concomitant with the stabilization of the mRNA, suggesting a postranscriptional level of control. Finally, the augmented expression of IL-2R gamma in IL-2- and IFN gamma-treated monocytes was associated with an increased IL-2...