Lymphotoxin beta receptor triggering induces activation of the nuclear factor beta B transcription factor in some cell types

NF kappa B is a pleiotropic transcription factor capable of activating the expression of a great variety of genes critical for the immunoinflammatory response. Tumor necrosis factor alpha (TNF alpha) and lymphotoxin alpha (LT alpha, originally TNF beta) are potent nuclear factor kappa B (NF kappa B) activators in various cell types. The LT alpha molecule, in addition to being secreted as a soluble trimer, can also form membrane-anchored heterotrimers with the LT beta chain, another member of the TNF family. The LT alpha 1 beta 2 heterotrimer binds a specific receptor, called the LT beta receptor (LT beta-R), which is also a member of the TNF receptor family. Here, we show that engagement of LT beta-R with a soluble form of LT alpha 1 beta 2 or with a specific anti-LT beta-R agonistic monoclonal antibody CBE11 quickly induces activation of NF kappa B in HT-29 and WiDr human adenocarcinomas. LT beta-R triggering activates NF kappa B and induces proliferation in WI-38 human lung fibroblasts. No NF kappa B activation is observed in human umbilical vein endothelial cells, correlating with the inability of LT beta-R activation to induce expression of NF kappa B-dependent cell surface adhesion molecules. Thus, like several other members of the TNF receptor family, the LT beta-R can activate NF kappa B following receptor ligation in some but not all LT beta-R-positive cells.