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  • FASEB J. 2013-08; NULL NULL NULL
  • Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling.

  • Moh MC, Lorenzini PA, Gullo C, Schwarz H.
  • Department of Physiology, †Immunology Program, ‡Department of Medical Education, Research, and Evaluation, Duke-National University of Singapore Graduate Medical School, §Department of Microbiology, and Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.

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...41B-436) antibody, while the cytoplasmic CD137L domain was detected with a custom-made anti-CD137L monoclonal antibody (Genscript, Piscataway, NJ, USA). Suspension cells were centrifuged onto glass slides using a cytospin. Fluorescence was visualized...


FASEB J.

Abstract

Reverse signaling through CD137 ligand (CD137L) potently activates monocytes. However, the underlying mechanism is not well elucidated. This study provides evidence that tumor necrosis factor receptor 1 (TNFR1) acts as a coreceptor for CD137L and mediates CD137L signaling. CD137L colocalizes with TNFR1 on the plasma membrane and binds directly to TNFR1 via its extracellular domain. Using the human monocytic THP-1 cell line, we demonstrate that engagement of CD137L by recombinant CD137 protein promotes cell adhesion, apoptosis, expression of CD14, and production of IL-8 and tumor necrosis factor (TNF). Concomitantly, the expression of TNFR1 protein is down-regulated in response to CD137L activation, due to enhanced extracellular release and internalization of TNFR1. Activation of TNFR1 by TNF protein additively augments CD137L-induced IL-8 expression. Conversely, inhibition of TNFR1 activity by a TNFR1-neutralizing antibody inhibits CD137L-mediated cell adhesion, cell death, CD14 expression, and IL-8 production. Taken together, these data show that TNFR1 associates with CD137L and is required for CD137L reverse signaling.-Moh, M. C., Lorenzini, P. A., Gullo, C., Schwarz, H. Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling.

Keywords

TNFR1; THP-1; cells monocytes

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...41B-436) antibody, while the cytoplasmic CD137L domain was detected with a custom-made anti-CD137L monoclonal antibody (Genscript, Piscataway, NJ, USA). Suspension cells were centrifuged onto glass slides using a cytospin. Fluorescence was visualized...

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