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A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes.

Publication ,  Journal Article
Zhu, B; Liu, Z; Wang, P; Wu, C; Xu, H
Published in: Transplant Proc
October 2008

Costimulatory molecules play critical roles during cell-mediated immune responses. We undertook this study to determine whether CD154-CD40 interactions induced human endothelial cell (EC) activation via the nuclear factor (NF)-kappaB pathway, and whether the upregulation of monocyte-derived CD40 and CD80 is NF-kappaB pathway dependent. A CD154-expressing D1.1 cell-EC coculture with or without the NF-kappaB inhibitor BAY11-7082 was established to examine EC activation as indicated by CD62E expression. Peripheral blood mononuclear cell (PBMC)-EC cocultures were performed in the presence or absence of BAY11-7082; the expression of CD40 and CD80 on monocytes was analyzed by FACS. Allogeneic mixed lymphocyte-EC reaction (MLER) was performed to determine the inhibitory effects of BAY11-7082 to prevent lymphocyte proliferation. FACS demonstrated upregulation of EC-derived CD62E expression induced by CD154 expressing D1.1 cells. BAY11-7082 pretreated EC failed to upregulate CD62E after interaction with D1.1 cells. Monocytes upregulated CD40 and CD80 expression during PBMC-HEC interaction, and BAY11-7082 suppressed monocyte-derived CD40 and CD80 expression in a dose-dependent manner. The monocyte-derived CD86 expression was downregulated by NF-kappaB inhibitor. BAY11-7082 demonstrated inhibition of lymphocyte proliferation of allogeneic MLER. This study demonstrated that the NF-kappaB inhibitor BAY11-7082 prevented CD154-CD40 interaction-induced EC activation, suggesting that the activation of EC by T-cell-derived CD154 is via NF-kappaB pathway. The NF-kappaB inhibitor suppressed upregulation of monocytederived CD40 and CD80. Additionally, BAY11-7082 suppressed lymphocyte proliferation in response to allogeneic EC. These data indicated that NF-kappaB plays an important role in regulating costimulatory molecules in allogeneic immune responses, and strengthens the rationale for the use of NF-kappaB-directed therapy in allotransplantation.

Duke Scholars

Published In

Transplant Proc

DOI

ISSN

0041-1345

Publication Date

October 2008

Volume

40

Issue

8

Start / End Page

2724 / 2728

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Sulfones
  • Recombinant Proteins
  • Nitriles
  • NF-kappa B
  • Monocytes
  • Lymphocyte Activation
  • Interferon-gamma
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, B., Liu, Z., Wang, P., Wu, C., & Xu, H. (2008). A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes. Transplant Proc, 40(8), 2724–2728. https://doi.org/10.1016/j.transproceed.2008.07.129
Zhu, B., Z. Liu, P. Wang, C. Wu, and H. Xu. “A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes.Transplant Proc 40, no. 8 (October 2008): 2724–28. https://doi.org/10.1016/j.transproceed.2008.07.129.
Zhu, B., et al. “A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes.Transplant Proc, vol. 40, no. 8, Oct. 2008, pp. 2724–28. Pubmed, doi:10.1016/j.transproceed.2008.07.129.
Journal cover image

Published In

Transplant Proc

DOI

ISSN

0041-1345

Publication Date

October 2008

Volume

40

Issue

8

Start / End Page

2724 / 2728

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Sulfones
  • Recombinant Proteins
  • Nitriles
  • NF-kappa B
  • Monocytes
  • Lymphocyte Activation
  • Interferon-gamma
  • Humans