Nerve Growth Factor Induces the Expression of Certain Cytokine Genes and bcl-2 in Mast Cells
POTENTIAL ROLE IN SURVIVAL PROMOTION*
- From the Departments of Neurology and Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110
- ↵‡To whom correspondence should be addressed: Dept. of Molecular Biology and Pharmacology, Campus Box 8103, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-3926; Fax: 314-362-7058; E-mail: ejohnson{at}pharmdec.wustl.edu.
Abstract
Nerve growth factor (NGF) promotes mast cell survival in vitro (Horigome, K., Bullock, E. D., and Johnson, E. M., Jr. (1994) J. Biol. Chem. 269, 2695-2702). NGF survival promotion is cell density-dependent, and conditioned medium experiments have shown that NGF increases the production of an autocrine mast cell survival activity. Cytokines are potential candidates for autocrine survival factors. In rat peritoneal mast cells (RPMC), NGF caused an increase in the messenger RNAs for interleukin (IL)-3, IL-4, IL-10, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor. This induction was NGF dose-dependent, was blocked by NGF-neutralizing antibodies, and was not observed in the non-mast peritoneal cell population. The immunosuppressive agent, cyclosporin A, blocked both cytokine induction and NGF-activated survival promotion but not survival promotion activated by IL-3 or stem cell factor, suggesting that NGF enhanced RPMC survival by increasing cytokine production. We also examine the effects of NGF on the expression levels of some members of the bcl-2 family and the interleukin-1β-converting enzyme-like cysteine protease families. NGF markedly increased bcl-2 expression but had little or no effect on the other genes studied. The induction of bcl-2 mRNA by NGF was not blocked by cyclosporin A. These data suggest that induced cytokine gene expression but not increased expression of bcl-2 mediates NGF-survival promotion in RPMC.
Footnotes
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↵* This work was supported by National Institutes of Health Grants RO1-NS24679, RO1-AG12947, and 5T32HL07275. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received May 30, 1996.
- Revision received August 19, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
