PMID- 18003981
OWN - NLM
STAT- MEDLINE
DCOM- 20081110
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 19
IP  - 2
DP  - 2008 Feb
TI  - Hypoxia-induced IL-18 increases hypoxia-inducible factor-1alpha expression 
      through a Rac1-dependent NF-kappaB pathway.
PG  - 433-44
AB  - 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-1alpha (HIF-1alpha). Mechanistically, 
      IL-18 induces HIF-1alpha through the activity of the GTPase Rac1, which inducibly 
      associates with the IL-18 receptor beta (IL-18Rbeta) subunit, via a 
      PI3K-AKT-NF-kappaB-dependent pathway. Importantly, the knockdown of the 
      IL-18Rbeta subunit inhibited IL-18-driven tumor cell metastasis. Collectively, 
      these findings demonstrate a feed-forward pathway in HIF-1alpha-mediated tumor 
      progression, in which the induction of IL-18 by hypoxia or inflammatory cells 
      augments the expression of both HIF-1alpha and tumor cell metastasis.
FAU - Kim, Jeongki
AU  - Kim J
AD  - Stem Cell Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yusong, Daejon 305-333, Republic of Korea.
FAU - Shao, Yan
AU  - Shao Y
FAU - Kim, Sang Yong
AU  - Kim SY
FAU - Kim, Seyl
AU  - Kim S
FAU - Song, Hyun Keun
AU  - Song HK
FAU - Jeon, Jun Ho
AU  - Jeon JH
FAU - Suh, Hyun Woo
AU  - Suh HW
FAU - Chung, Jin Woong
AU  - Chung JW
FAU - Yoon, Suk Ran
AU  - Yoon SR
FAU - Kim, Young Sang
AU  - Kim YS
FAU - Choi, Inpyo
AU  - Choi I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071114
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-18)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Interleukin-18)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/drug effects
MH  - Cell Line
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Interleukin-18/*genetics/metabolism/pharmacology
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Neoplasm Metastasis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Interleukin-18/metabolism
MH  - Signal Transduction/drug effects
MH  - Transcription, Genetic/drug effects
MH  - rac1 GTP-Binding Protein/*metabolism
PMC - PMC2230593
EDAT- 2007/11/16 09:00
MHDA- 2008/11/11 09:00
PMCR- 2008/04/05
CRDT- 2007/11/16 09:00
PHST- 2007/11/16 09:00 [pubmed]
PHST- 2008/11/11 09:00 [medline]
PHST- 2007/11/16 09:00 [entrez]
PHST- 2008/04/05 00:00 [pmc-release]
AID - E07-02-0182 [pii]
AID - 3296580 [pii]
AID - 10.1091/mbc.e07-02-0182 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2008 Feb;19(2):433-44. doi: 10.1091/mbc.e07-02-0182. Epub 2007 Nov 
      14.