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

  • Jihye Kim
  • , Cherlhyun Kim
  • , Tae Sung Kim
  • , Sa Ik Bang
  • , Young Yang
  • , Hyunjeong Park*
  • , Daeho Cho
  • *Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    63 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1284-1289
    Number of pages6
    JournalBiochemical and biophysical research communications
    Volume344
    Issue number4
    DOIs
    Publication statusPublished - 2006 Jun 16

    Bibliographical note

    Funding Information:
    This work was supported by the Korea Science and Engineering Foundation (KOSEF) through Research Center for Women’s Diseases (R11-2005-017) at Sookmyung Women’s University, TIMRC at SNU (R13-2002-025-01002-0) and Korea Research Foundation Grant (KRF-2004-042-E00055).

    Keywords

    • Gastric cancer
    • IL-18
    • JNK pathway
    • TSP-1

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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