Dissociation of Cytokine Signals for Proliferation and Apoptosis

Yufang Shi, Ruoxiang Wang, Ajay Sharma, Chuan Gao, Mary Collins, Linda Penn, Gordon B. Mills

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    Abstract

    Cytokines such as IL-2 or IL-3 prevent cell death through apoptosis, either by preventing apoptosis directly or by sensitizing cells to survival factors present in serum. We demonstrate herein that BAF-B03 cells transfected with the wild-type IL-2R β-chain undergo apoptosis when stimulated with IL-2 or IL-3 in the absence of serum. IL-2 also induced apoptosis in normal IL-2-responsive human T cell blasts in the absence of serum, and furthermore, epidermal growth factor and fibroblast growth factor induced increased rates of apoptosis in fibroblasts in the absence of serum, suggesting that cytokine-induced apoptosis in the absence of serum survival factors might represent an important biologic phenomenon. In the presence or the absence of serum, IL-2 and IL-3 induced expression of both c-Myc and Bax. In contrast, optimal cytokine-induced expression of Bcl-2 requires serum. Constitutive expression of Bcl-2 prevented cytokine-induced apoptosis. Transferrin mimicked serum by inducing an increase in Bcl-2 expression levels and concurrently prevented apoptosis. These results suggest that the balance between cytokine- and serum-induced Bcl-2 expression and cytokine-induced Bax expression may determine whether a cell undergoes cytokine-induced apoptosis. In BAF/BO3 cells expressing a mutant IL-2Rβ with a deletion of the acidic domain, IL-2 did not induce either Bax expression or apoptosis. This suggests that the acidic domain of the IL-2R β-chain plays an essential role in regulating IL-2-mediated Bax expression and apoptosis. Cytokine-induced apoptosis and its counterbalance by survival factors present in serum may play an important role in the regulation of cellular homeostasis during pathophysiologic processes.

    Original languageEnglish (US)
    Pages (from-to)5318-5328
    Number of pages11
    JournalJournal of Immunology
    Volume159
    Issue number11
    StatePublished - Dec 1 1997

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Shi, Y., Wang, R., Sharma, A., Gao, C., Collins, M., Penn, L., & Mills, G. B. (1997). Dissociation of Cytokine Signals for Proliferation and Apoptosis. Journal of Immunology, 159(11), 5318-5328.