c-jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)-6-induced vascular endothelial growth factor (VEGF) production: Cyclosporine a partially mimics this inhibitory effect

Koji Naruishi, Fusanori Nishimura, Hisa Yamada-Naruishi, Kazuhiro Omori, Mayumi Yamaguchi, Shogo Takashiba

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Angiogenesis is a common complication of organ-transplant rejection. One of the primary responsible molecules for enhanced angiogenesis is vascular endothelial growth factor (VEGF). Activated protein (AP)-1 is considered to play a key role in the transcription of VEGF. c-jun N-terminal kinase (JNK), one of the MAP kinase family members, plays a critical role in AP-1 activation. Thus, we tested the effect of a novel JNK inhibitor, SP600125, on VEGF production in fibroblasts. SP600125 significantly suppressed interleukin (IL)-6-induced production of VEGF in cultured fibroblasts. Cyclosporine A (CsA), a known in vitro antiangiogenic reagent, partially mimicked this suppression. In fact, CsA suppressed IL-6-induced phosphorylation of JNK. The results indicate that although both SP600125 and CsA are anti-angiogenic by inhibiting VEGF production by way of a JNK-dependent pathway, the inhibitory effect was much stronger with the novel inhibitor of JNK than with CsA.

Original languageEnglish
Pages (from-to)1380-1382
Number of pages3
JournalTransplantation
Volume76
Issue number9
DOIs
Publication statusPublished - Nov 15 2003

ASJC Scopus subject areas

  • Transplantation

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