Open AccessC-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
Author(s) -
Koji Naruishi,
Fusanori Nishimura,
Hisa Yamada-Naruishi,
Kazuhiro Omori,
Mayumi Yamaguchi,
Shogo Takashiba
Publication year - 2003
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/01.tp.0000085661.52980.95
Subject(s) - vascular endothelial growth factor , angiogenesis , kinase , c jun , cancer research , vascular endothelial growth factor a , chemistry , microbiology and biotechnology , phosphorylation , mitogen activated protein kinase , biology , vegf receptors , transcription factor , biochemistry , gene
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 anti-angiogenic 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.