Pathological activation of canonical nuclear-factor κB by synergy of tumor necrosis factor α and TNF-like weak inducer of apoptosis in mouse acute colitis.

摘要: Tumor necrosis factor (TNF)-α is a major effector in various inflammatory conditions. TNF-like weak inducer of apoptosis (TWEAK) member the TNF superfamily that promotes tissue damage through its receptor, FGF-inducible molecule 14 (Fn14). Since both TWEAK and TNF-α have been shown to mediate pathological responses inter-dependent or independent pathways by vitro, potential interplay these was investigated mouse colitis model. Acute induced rectal injection trinitrobenzene sulfonic acid (TNBS), with administration control IgG, receptor (TNFR)-Ig chimeric protein, anti-TWEAK monoclonal antibody, combination TNFR-Ig antibody. On day 4, disease severity evaluated gene expression profiling analyzed using whole colon tissue. NF-κB activation Western blot. Levels transcript TWEAK, Fn14 NF-κB-related molecules were measured purified epithelial cells (ECs). As result, canonical (p50/RelA), but not noncanonical (p100/RelB)-mediated pathway hallmark this Inflammation upregulation only ECs other cell types. Combination treatment antibody synergistically reduced comparison single agent treatment. Gene profile indicated downregulation In conclusion, synergistic critical for induction acute inflammation.