IL-4 and Insulin-Like Growth Factor-I Inhibit the Decline in Bcl-2 and Promote the Survival of IL-3-Deprived Myeloid Progenitors

Christian Minshall, Sean Arkins, James Straza, James Conners, Robert Dantzer, Gregory G. Freund, Keith W. Kelley

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The proto-oncogene product Bcl-2 regulates cell survival in both the immune and central nervous systems. We withdrew growth factors from IL-3-dependent murine myeloid progenitor cells (factor dependent cell progenitors (FDCP)) and measured a time-dependent 80% reduction in endogenous expression of Bcl-2. This decline in Bcl-2 is directly associated with a fourfold increase in the apoptotic population after 12 h and an eightfold increase after 24 h. Since IL-4 and insulin-like growth factor-I (IGF-I) regulate myeloid cell growth, we used IL-3-deprived FDCP cells to determine whether IL-4 and IGF-I maintain Bcl-2 expression and prevent apoptosis. We demonstrate that IL-4, like IGF-I and IL-3, promotes survival of FDCP cells by reducing the apoptotic population. Flow cytometric measurement of intracellular Bcl-2 established that IL-4 and IGF-I maintain 10-fold higher levels of Bcl-2 than in IL-3-deprived cells. Similarly, Western analysis of Bcl-2 in lysates of IL-3-deprived myeloid progenitors confirmed that both IL-4 and IGF-I share with IL-3 the ability to maintain intact Bcl-2 protein. However, IL-4 and IGF-I do not change expression of the apoptotic inducer, Bax, although they maintain high levels of Bcl-2 that coimmunoprecipitate with Bax. Collectively, these data demonstrate that IL-4 and IGF-I, like IL-3, inhibit apoptosis in myeloid progenitors and maintain high levels of Bcl-2/Bax heterodimers, suggesting that Bcl-2 is a critical convergence point in the signaling pathways used by IL-4 and IGF-I.

Original languageEnglish (US)
Pages (from-to)1225-1232
Number of pages8
JournalJournal of Immunology
Volume159
Issue number3
StatePublished - Aug 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Minshall, C., Arkins, S., Straza, J., Conners, J., Dantzer, R., Freund, G. G., & Kelley, K. W. (1997). IL-4 and Insulin-Like Growth Factor-I Inhibit the Decline in Bcl-2 and Promote the Survival of IL-3-Deprived Myeloid Progenitors. Journal of Immunology, 159(3), 1225-1232.