TNFinduced

TNFinduced refers to cellular responses initiated by the cytokine tumor necrosis factor (TNF). It predominantly involves binding of TNF to TNF receptor 1 (TNFR1) and, to a lesser extent, TNFR2, triggering diverse signaling networks that regulate inflammation, survival, and cell fate.

Upon TNF binding, receptor-associated complex I forms at the membrane, activating NF-κB, MAPK, and transcription of anti-apoptotic genes. This promotes cell survival and inflammatory gene expression. Under conditions of impaired NF-κB signaling or caspase-8 inhibition, the signal can transition to death pathways. The cytosolic complex II can assemble, activating caspase-8 and leading to apoptosis. Alternatively, when RIPK3 and MLKL are engaged, necroptosis may occur, a lytic form of cell death. The outcome is tightly regulated by ubiquitination status of RIPK1 and the balance between pro-survival and pro-death signals.

Physiological relevance includes host defense and tissue homeostasis; dysregulated TNF signaling is implicated in inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and sepsis. In cancer, TNF-induced inflammation can have pro-tumorigenic effects, while TNF signaling can also contribute to anti-tumor cell death under certain therapies.

Therapeutic relevance: Anti-TNF agents are used to treat autoimmune inflammatory diseases by dampening TNF-induced signaling; risks include infection and demyelinating events. Research continues on selective modulation of TNF pathways to separate beneficial anti-inflammatory effects from adverse outcomes.