Interleukin-4 mediates cell growth inhibition through activation of Stat1

Theresa Li Yun Chang, Xianbu Peng, Xin Yuan Fu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Interleukin-4 (IL-4) activates Stat6 (signal transducer and activator of transcription 6) and plays multiple roles in regulation of the immune system. IL-4 also triggers phosphorylation of insulin receptor substrate (IRS), leading to stimulation of cell growth. Moreover, IL-4 inhibits proliferation of a variety of cells, but the molecular mechanism of its growth inhibitory effect is not understood. In this study, we demonstrated that IL-4 inhibited cell growth of colon carcinoma cell lines (HT29 and WiDr) but promoted cell growth of Burkitt's lymphoma cell lines (BL30 and BL41) in a dose-dependent manner. The growth inhibition was not dependent on Stat6 activation, because Stat6 was activated at similar levels in all cell lines in response to IL-4. Strikingly, IL-4 activated Stat1 in colon carcinoma cell lines but not in Burkitt's lymphoma cell lines. Therefore, these results suggest that IL-4 induced Stat1 activation, resulting in growth inhibition of colon carcinoma cell lines. Importantly, we present evidence that Stat1 is necessary for IL- 4-mediated growth inhibition using Stat1-deficient and Stat1-reconstituted cells. The growth inhibitory effect of IL-4 was diminished in Stat1-deficient cells, whereas it was restored in Stat1-reconstituted cells. In addition, the expression of dominant-negative Stat1 in HT29 cells led to the loss of growth inhibition in response to IL-4. Taken together, our data suggest that IL-4 activates Stat1, leading to cell growth inhibition in colon cancer cells. Thus, this study demonstrates, for the first time, a molecular mechanism by which IL-4 inhibits cell growth.

Original languageEnglish (US)
Pages (from-to)10212-10217
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number14
DOIs
StatePublished - Apr 7 2000
Externally publishedYes

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Cell growth
Interleukin-4
Chemical activation
Growth
Cells
STAT6 Transcription Factor
Cell Line
Colon
Burkitt Lymphoma
Carcinoma
HT29 Cells
Phosphorylation
Immune system
Insulin Receptor
Colonic Neoplasms
Transcriptional Activation
Immune System

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interleukin-4 mediates cell growth inhibition through activation of Stat1. / Chang, Theresa Li Yun; Peng, Xianbu; Fu, Xin Yuan.

In: Journal of Biological Chemistry, Vol. 275, No. 14, 07.04.2000, p. 10212-10217.

Research output: Contribution to journalArticle

Chang, Theresa Li Yun ; Peng, Xianbu ; Fu, Xin Yuan. / Interleukin-4 mediates cell growth inhibition through activation of Stat1. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 14. pp. 10212-10217.
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