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

Fingerprint

JNK Mitogen-Activated Protein Kinases
Vascular Endothelial Growth Factor A
Cyclosporine
Interleukin-6
Fibroblasts
Mitogen-Activated Protein Kinase Kinases
Graft Rejection
Proteins
Phosphorylation
anthra(1,9-cd)pyrazol-6(2H)-one
Transplants

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

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

In: Transplantation, Vol. 76, No. 9, 15.11.2003, p. 1380-1382.

Research output: Contribution to journalArticle

@article{3e92c87aec3d4f67b6bccf5cc65e98e5,
title = "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",
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.",
author = "Koji Naruishi and Fusanori Nishimura and Hisa Yamada-Naruishi and Kazuhiro Omori and Mayumi Yamaguchi and Shogo Takashiba",
year = "2003",
month = "11",
day = "15",
doi = "10.1097/01.TP.0000085661.52980.95",
language = "English",
volume = "76",
pages = "1380--1382",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - c-jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)-6-induced vascular endothelial growth factor (VEGF) production

T2 - Cyclosporine a partially mimics this inhibitory effect

AU - Naruishi, Koji

AU - Nishimura, Fusanori

AU - Yamada-Naruishi, Hisa

AU - Omori, Kazuhiro

AU - Yamaguchi, Mayumi

AU - Takashiba, Shogo

PY - 2003/11/15

Y1 - 2003/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0242660123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242660123&partnerID=8YFLogxK

U2 - 10.1097/01.TP.0000085661.52980.95

DO - 10.1097/01.TP.0000085661.52980.95

M3 - Article

C2 - 14627919

AN - SCOPUS:0242660123

VL - 76

SP - 1380

EP - 1382

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 9

ER -