Hypoxia-induced IL-18 increases hypoxia-inducible factor-1α expression through a Rac1-dependent NF-κB pathway

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Title
Hypoxia-induced IL-18 increases hypoxia-inducible factor-1α expression through a Rac1-dependent NF-κB pathway
Author(s)
J Kim; Y Shao; S Y Kim; S Kim; H K Song; J H Jeon; Hyun Woo Suh; Jin Woong Chung; Suk Ran Yoon; Y S Kim; In Pyo Choi
Bibliographic Citation
Molecular Biology of Cell, vol. 19, no. 2, pp. 433-444
Publication Year
2008
Abstract
Interleukin-18 (IL-18) plays pivotal roles in linking inflammatory immune responses and tumor progression and metastasis, yet the manner in which this occurs remains to be sufficiently clarified. Here we report that hypoxia induces the transcription and secretion of IL-18, which subsequently induces the expression of hypoxia-inducible factor-1α (HIF-1α). Mechanistically, IL-18 induces HIF-1α through the activity of the GTPase Rac1, which inducibly associates with the IL-18 receptor β (IL-18Rβ) subunit, via a PI3K-AKT-NF-κB-dependent pathway. Importantly, the knockdown of the IL-18Rβ subunit inhibited IL-18-driven tumor cell metastasis. Collectively, these findings demonstrate a feed-forward pathway in HIF-1α-mediated tumor progression, in which the induction of IL-18 by hypoxia or inflammatory cells augments the expression of both HIF-1α and tumor cell metastasis.
ISSN
1059-1524
Publisher
Amer Soc Cell Biology
DOI
http://dx.doi.org/10.1091/mbc.E07-02-0182
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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