Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells

  • Authors:
    • Ko-ichi Kawahara
    • Teruto Hashiguchi
    • Kiyoshi Kikuchi
    • Salunya Tancharoen
    • Naoki Miura
    • Takashi Ito
    • Yoko Oyama
    • Yuko Nawa
    • Kamal K. Biswas
    • Xiaojie Meng
    • Yoko Morimoto
    • Binita Shrestha
    • Hisayo Sameshima
    • Ikuro Maruyama
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/ijmm_00000066
  • Pages: 639-644
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Abstract

High mobility group box 1 (HMGB1) is a non-histone nuclear protein which is released from the nucleus of activated macrophages into the extracellular space in response to stimuli such as endotoxin or necrosis. The HMGB1 functions as a potent proinflammatory cytokine in the extracellular spaces. Recently, HMGB1 has been implicated in the progression of atherosclerosis. However, the association between HMGB1 and the development of atherosclerosis is poorly understood. Therefore, we examined whether serotonin (5-HT), a key factor involved in the development of atherosclerosis, induced HMGB1 release in human umbilical vein endothelial cells (HUVECs). We found that 5-HT induced the release of HMGB1 but not of ERK1/2 and JNK from HUVECs via the 5-HT receptor (5-HT1B)/p38 mitogen-activated protein kinase (MAPK) signaling pathway. The p38MAPK inhibitor SB203580 and the 5-HT1B antagonist GR55526 markedly inhibited HMGB1 release from 5-HT-stimulated HUVECs. The vascular endothelial growth factor (VEGF) derived from activated macrophages in atherosclerotic lesions also plays an important role in the progression of atherosclerosis. We found that HMGB1 induced VEGF production in macrophage-like RAW264.7 cells. HMGB1 induced the activation of p38MAPK, ERK1/2 and Akt. The PI3-kinase inhibitor LY294002 significantly inhibited VEGF production in HMGB1-stimulated macrophages, while other kinase inhibitors did not. These results suggest that HMGB1 release may contribute as a risk factor in the development and progression of atherosclerosis.

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November 2008
Volume 22 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kawahara K, Hashiguchi T, Kikuchi K, Tancharoen S, Miura N, Ito T, Oyama Y, Nawa Y, Biswas KK, Meng X, Meng X, et al: Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells. Int J Mol Med 22: 639-644, 2008
APA
Kawahara, K., Hashiguchi, T., Kikuchi, K., Tancharoen, S., Miura, N., Ito, T. ... Maruyama, I. (2008). Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells. International Journal of Molecular Medicine, 22, 639-644. https://doi.org/10.3892/ijmm_00000066
MLA
Kawahara, K., Hashiguchi, T., Kikuchi, K., Tancharoen, S., Miura, N., Ito, T., Oyama, Y., Nawa, Y., Biswas, K. K., Meng, X., Morimoto, Y., Shrestha, B., Sameshima, H., Maruyama, I."Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells". International Journal of Molecular Medicine 22.5 (2008): 639-644.
Chicago
Kawahara, K., Hashiguchi, T., Kikuchi, K., Tancharoen, S., Miura, N., Ito, T., Oyama, Y., Nawa, Y., Biswas, K. K., Meng, X., Morimoto, Y., Shrestha, B., Sameshima, H., Maruyama, I."Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells". International Journal of Molecular Medicine 22, no. 5 (2008): 639-644. https://doi.org/10.3892/ijmm_00000066