Please use this identifier to cite or link to this item: https://doi.org/10.1096/fj.12-225250
Title: Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling
Authors: Moh, M.C.
Lorenzini, P.A.
Gullo, C. 
Schwarz, H.
Keywords: Monocytes
THP-1 cells
TNFR1
Issue Date: Aug-2013
Citation: Moh, M.C., Lorenzini, P.A., Gullo, C., Schwarz, H. (2013-08). Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling. FASEB Journal 27 (8) : 2957-2966. ScholarBank@NUS Repository. https://doi.org/10.1096/fj.12-225250
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. © FASEB.
Source Title: FASEB Journal
URI: http://scholarbank.nus.edu.sg/handle/10635/110336
ISSN: 15306860
DOI: 10.1096/fj.12-225250
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