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Interferon-gamma induced proliferation of human myeloid leukaemia cell lines
H G Drexler1, M Zaborski, H Quentmeier
1DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Insights
Interferon-gamma (IFN-gamma) stimulates the proliferation of certain myeloid leukemia cells, acting as a survival factor and modulating responses to other cytokines. This suggests a potential role in leukemia progression and normal hematopoiesis regulation.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Interferon-gamma (IFN-gamma) is a cytokine with diverse immune functions, including antiviral and antiproliferative activities.
- Its role in regulating cell proliferation, particularly in the context of leukemia, requires further investigation.
Purpose of the Study:
- To investigate the effect of IFN-gamma on the proliferation of human leukemia cell lines.
- To determine if IFN-gamma can modulate the proliferative responses to other cytokines and act as a survival factor.
Main Methods:
- Utilized continuous human leukemia cell lines for proliferation assays.
- Employed anti-IFN-gamma monoclonal antibody for neutralization studies.
- Performed flow cytometry to analyze IFN-gamma receptor expression.
- Assessed effects on apoptosis under serum-free conditions.
Main Results:
- IFN-gamma significantly stimulated proliferation in 11/19 growth factor-dependent leukemia cell lines (EC50: 0.1-0.6 ng/ml).
- IFN-gamma receptor expression varied (37-97%) across cell lines.
- IFN-gamma showed variable effects on cytokine-induced proliferation and suppressed apoptosis, acting as a survival factor.
- Proliferation induction correlated with STAT 1 activation.
Conclusions:
- IFN-gamma can induce proliferation and modulate cytokine responses in myeloid leukemia cells, suggesting pathological relevance in vivo.
- IFN-gamma may act as a bifunctional regulator of hematopoietic cell proliferation in physiological settings, influenced by microenvironmental signals.
Abstract:
Interferon-gamma (IFN-gamma) is a pleiotropic cytokine involved in the regulation of various phases of immune and inflammatory responses; it also has anti-viral and anti-proliferative activity. Using continuous human leukaemia cell lines as model systems, we found that IFN-gamma stimulated the proliferation of leukaemic myeloid cells; this effect was specifically neutralized by an anti-IFN-gamma monoclonal antibody (McAb). No proliferative response was seen in autonomously growing cell lines; however, 11/19 constitutively growth factor-dependent cell lines showed a significant response in short-term proliferation assays upon incubation with IFN-gamma. The stimulation indices ranged from 2 to 37 compared with the untreated control cells; the EC50 values for these cell lines were in the range of 0.1-0.6 ng/ml IFN-gamma. Flow cytometric analysis demonstrated heterogeneity in the expression of the IFN-gamma receptor, as it was found on 37-97% of the cells per cell line. The effects of IFN-gamma on proliferation triggered by a spectrum of 10 other cytokines were variable, and both stimulation and attenuation of the proliferative responses were seen in different cell lines. Under serum-free culture conditions, IFN-gamma acted as a survival factor suppressing apoptosis. As has been described for other functional processes triggered by IFN-gamma, the proliferation-inducing activity of IFN-gamma also led to activation of the signal transducing element STAT 1. Thus, IFN-gamma can induce myeloid leukaemia cells to proliferate and can modulate their proliferative response to other cytokines. Therefore IFN-gamma may be a pathologically relevant ligand for leukaemic cell proliferation in vivo. In physiological settings, IFN-gamma might be a bifunctional regulator of haemopoietic cell proliferation, depending on other differential co-signals from the micro-environment.
