IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway

IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-06, Vol.344 (4), p.1284-1289
Main Authors: Kim, Jihye, Kim, Cherlhyun, Kim, Tae Sung, Bang, Sa Ik, Yang, Young, Park, Hyunjeong, Cho, Daeho
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Cell Line, Tumor
Enzyme Activation - drug effects
ENZYME IMMUNOASSAY
Gastric cancer
Humans
IL-18
Interleukin-18 - pharmacology
JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases - drug effects
JNK Mitogen-Activated Protein Kinases - metabolism
JNK pathway
MELANOMAS
METASTASES
Phosphorylation - drug effects
POLYMERASE CHAIN REACTION
PROTEINS
RNA, Messenger - metabolism
Stomach Neoplasms - enzymology
Stomach Neoplasms - metabolism
Thrombospondin 1 - genetics
Thrombospondin 1 - metabolism
TIME DEPENDENCE
TOTAL SUSPENDED PARTICULATES
TSP-1
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Summary:IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported that it stimulates angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related to tumor proliferation and metastasis. This study investigated the relationship between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1 protein production by IL-18 increased in both a dose- and time-dependent manner. The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in TSP-1 expression involving JNK.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.04.016