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[an acronym derived from: homologous to lymphotoxins, inducible expression, competes with HSV glycoprotein D for HVEM, a receptor expressed on T-lymphocytes].
LIGHT is a member of the TNF cytokine family. Based on its homology with other members of the TNF ligand protein superfamily the protein is referred to also as TNFSF14 [TNF ligand superfamily member 14] and is identical with HVEM ligand. In the nomenclature of CD antigens it has been given the designation CD258.
The gene was isolated from a cDNA library prepared from activated T-cells (Mauri et al, 1998). LIGHT mRNA is expressed highly in splenocytes, activated peripheral blood lymphocytes, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and several tumor cells examined.
LIGHT, which is a 29 kDa type II transmembrane protein (240 amino acids), has been shown to trigger distinct biological responses in target cells, depending upon the expression patterns of its receptors. LIGHT protein causes cell death by apoptosis of various tumor cells expressing both LT-beta receptor and HVEM receptors. Its cytotoxicity can be blocked specifically by addition of a LT-beta receptor-Fc or a TR2-HVEM-Fc fusion protein. IFN-gamma greatly enhances apoptosis mediated by LIGHT. LIGHT is not cytolytic for tumor cells expressing only the LT-beta receptor or HVEM (TR2). It also is not cytolytic for hematopoietic cells expressing only HVEM, such as peripheral blood lymphocytes, Jurkat cells, or CD8(+) tumor infiltrating lymphocytes. Treatment of activated peripheral blood lymphocytes with LIGHT causes the release of IFN-gamma. Morel et al (2000) have shown that the expression of LIGHT is upregulated, whereas expression of its receptor, HVEM, is downregulated after cell activation of T-cells.
Anand et al (2006) have shown that LIGHT, through interaction with the lymphotoxsin-beta receptor, is upregulated and functions as a pro-inflammatory cytokine in two independent experimental hepatitis models. Monoclonal antibodies that interfere with signaling through the receptor protect mice from lethal hepatitis.
Edwards et al (2006) have reported that LIGHT promotes osteoclast formation from human peripheral blood mononuclear cells and murine macrophage precursors mediated by RANKL and can can induce osteoclast formation by a mechanism independent of RANKL. Increased concentrations of LIGHT arefound in patients with rheumatoid arthritis.
Zhang et al (2003) have reported that LIGHT treatment of MDA-MB-231 breast cancer cells downregulates expression of anti-apoptosis proteins such as BCL2, BCLxL, BAG-1, and Mcl-1 and upregulates expression of the pro-apoptosis proteins BAK, BAD, but downregulates the pro-apoptosis protein BAX. LIGHT treatment also activates caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, DFF-45, and PARP1. The caspase-3 inhibitor, zDEVD-fmk and the broad range caspase inhibitor zVAD-fmk do not block apoptosis induced by LIGHT and IFN-gamma in MDA-MB-231 cells, showing that the activation of caspases is not required for LIGHT-induced apoptosis.
For other entries pertaining to cell death mechanisms see also the Apoptosis and Cell Death Dictionary section of this encyclopedia.
Copyright © 2012 by H IBELGAUFTS. All rights reserved.
ENTRY LAST MODIFIED: January 2006
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