Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice

  • Authors:
    • Jung Eun Lee
    • Ae Sin Lee
    • Duk Hoon Kim
    • Yu Jin Jung
    • Sik Lee
    • Byung-Hyun Park
    • Sun Hwa Lee
    • Sung Kwang Park
    • Won Kim
    • Kyung Pyo Kang
  • View Affiliations

  • Published online on: February 16, 2012     https://doi.org/10.3892/ijmm.2012.920
  • Pages: 864-870
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Abstract

Vascular endothelial cells play an important role in leukocyte trafficking during the inflammatory process. Proinflammatory cytokines activate the expression of cell adhesion molecules in endothelial cells. Janus kinase (JAK) and signal transducer and activator of transcription (STAT) are important intracellular cytokine signaling molecules that are involved in immune responses. The purpose of this study was to investigate the effect of JAK3 inhibition on the expression of tumor necrosis factor (TNF)-α-induced cell adhesion molecules in vascular endothelial cells and to evaluate the therapeutic potential of JAK3 for myocardial vascular permeability in endotoxemic mice. A JAK3 inhibitor, JANEX-1, decreased the TNF-α-induced expression of intercellular adhesion molecule (ICAM)-1, VCAM (vascular cell adhesion molecule)-1 and fractalkine in human umbilical vein endothelial cells (HUVECs). The downregulation of the expression of these cell adhesion molecules by JANEX-1 was mediated via suppression of STAT3 phosphorylation and nuclear factor-κB (NF-κB) activation. In endotoxemic mice, pretreatment with JANEX-1 prevented not only an increase in the cardiac ICAM-1 expression by LPS in the arteriolar and capillary endothelial cells, but also myocardial vascular leakage. These results suggest that inhibition of the JAK/STAT pathway by JANEX-1 ameliorates the expression of TNF-α-induced cell adhesion molecules in HUVECs and improves myocardial vascular permeability.

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May 2012
Volume 29 Issue 5

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

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Spandidos Publications style
Lee JE, Lee AS, Kim DH, Jung YJ, Lee S, Park B, Lee SH, Park SK, Kim W, Kang KP, Kang KP, et al: Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice. Int J Mol Med 29: 864-870, 2012
APA
Lee, J.E., Lee, A.S., Kim, D.H., Jung, Y.J., Lee, S., Park, B. ... Kang, K.P. (2012). Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice. International Journal of Molecular Medicine, 29, 864-870. https://doi.org/10.3892/ijmm.2012.920
MLA
Lee, J. E., Lee, A. S., Kim, D. H., Jung, Y. J., Lee, S., Park, B., Lee, S. H., Park, S. K., Kim, W., Kang, K. P."Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice". International Journal of Molecular Medicine 29.5 (2012): 864-870.
Chicago
Lee, J. E., Lee, A. S., Kim, D. H., Jung, Y. J., Lee, S., Park, B., Lee, S. H., Park, S. K., Kim, W., Kang, K. P."Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor‑α‑induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice". International Journal of Molecular Medicine 29, no. 5 (2012): 864-870. https://doi.org/10.3892/ijmm.2012.920