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 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.
Kim
Jihye
J
Department of Life Science, Sookmyung Women's University, Seoul, South Korea.
Kim
Cherlhyun
C
Kim
Tae Sung
TS
Bang
Sa Ik
SI
Yang
Young
Y
Park
Hyunjeong
H
Cho
Daeho
D
D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*
D020382:Interleukin-18; D012333:RNA, Messenger; D019700:Thrombospondin 1; D048031:JNK Mitogen-Activated Protein Kinases