Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor (*)
- From the (1)Department of Food Engineering and Biotechnology
- (2)Department of Biology, Technion, Israel Institute of Technology, Haifa 32000, Israel
- § To whom correspondence should be addressed: Dept. of Food Engineering & Biotechnology, Technion, Technion City, Haifa 32,000, Israel. Tel.: 972-4-293345; Fax: 972-4-320742; FOBENZI{at}TECHUNIX.TECHNION.AC.IL.
Abstract
Angiogenesis, the formation of new blood vessels, is induced by various growth factors and cytokines that act either directly or indirectly. Vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and therefore has a central role in physiological events of angiogenesis. Interleukin-6 (IL-6) expression on the other hand is elevated in tissues that undergo active angiogenesis but does not induce proliferation of endothelial cells. We demonstrate using Northern analysis that treatment of various cell lines with IL-6 for 6-48 h results in a significant induction of VEGF mRNA. The level of induction is comparable to the documented induction of VEGF mRNA by hypoxia or cobalt chloride, an activator of hypoxia-induced genes. In addition, it is demonstrated by transient transfection assays that the effect of IL-6 is mediated not only by DNA elements at the promoter region but also through specific motif(s) located in the 5′-untranslated region (5′-UTR) of VEGF mRNA. Our results imply that IL-6 may induce angiogenesis indirectly by inducing VEGF expression. It is also shown that the 5′-UTR is important for the expression of VEGF. The 5′-UTR of VEGF is exceptionally long (1038 base pairs) and very rich in G + C. This suggests that secondary structures in the 5′-UTR might be essential for VEGF expression through transcriptional and post-transcriptional control mechanisms.
Footnotes
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↵* This work was supported in part by grants from the Technion-Otto Meyerhof Biotechnology Laboratories (to B. Z. L.), the Israeli Ministry of Health (to B. Z. L. and G. N.), and The German-Israeli Foundation for Scientific Research and Development (to G. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- TNF-α
-
tumor necrosis factor-α
- IL-6
-
interleukin-6
- IL-6-RE
-
IL-6 response element
- 5′-UTR
-
5′-untranslated region
- VEGF
-
vascular endothelial growth factor
- CAT
-
chloramphenicol acetyltransferase
- PDGF
-
platelet-derived growth factor
- TGF-β
-
transforming growth factor-β
- EGF
-
epidermal growth factor
- IL-1β
-
interleukin-1β
- IFN-β
-
interferon-β
- bp
-
base pair(s)
- kb
-
kilobase pair(s)
- FGF
-
fibroblast growth factor.
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- Received July 17, 1995.
- Revision received October 25, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
