Lymphotoxin β receptor triggering induces activation of the nuclear factor κb transcription factor in some cell types

Abstract

NFκB is a pleiotropic transcription factor capable of activating the expression of a great variety of genes critical for the immunoinflammatory response. Tumor necrosis factor α (TNFα) and lymphotoxin α (LTα, originally TNFβ) are potent nuclear factor κB (NFκB) activators in various cell types. The LTα molecule, in addition to being secreted as a soluble trimer, can also form membrane-anchored heterotrimers with the LTβ chain, another member of the TNF family. The LTα1β2 heterotrimer binds a specific receptor, called the LTβ receptor (LTβ-R), which is also a member of the TNF receptor family. Here, we show that engagement of LTβ-R with a soluble form of LTα1β2 or with a specific anti-LTβ-R agonistic monoclonal antibody CBEll quickly induces activation of NFκB in HT-29 and WiDr human adenocarcinomas. LTβ-R triggering activates NFκB and induces proliferation in WI-38 human lung fibroblasts. No NFκB activation is observed in human umbilical vein endothelial cells, correlating with the inability of β-R activation to induce expression of NFκB-dependent cell surface adhesion molecules. Thus, like several other members of the TNF receptor family, the LTβ-R can activate NFκB following receptor ligation in some but not all LTβ-R-positive cells.