Pro-inflammatory cytokine signaling via Nuclear factor kappa-light-chain-enhancer of activated B cells and Mitogen-activated protein kinase pathways (NF-κB/MAPK signaling)

Pro-inflammatory cytokine signaling via the NF-κB and MAPK pathways is a complex intracellular communication network that mediates the cellular response to external inflammatory stimuli, such as TNF-α and IL-1β (Liu et al., 2017). Upon receptor activation, the NF-κB pathway proceeds through the IKK complex to release NF-κB dimers for nuclear translocation, while the MAPK pathways (p38, JNK, and ERK) utilize a three-tier kinase cascade to activate transcription factors like AP-1 (Zhang & Cao, 2019). Together, these pathways coordinately regulate the expression of hundreds of genes involved in the immune response, cell proliferation, and survival (Arthur & Ley, 2013). Chronic overactivation of these signaling axes is a primary driver of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis (Kyriakis & Avruch, 2012). Pharmacological strategies include the use of monoclonal antibodies to neutralize upstream cytokines or small molecule inhibitors targeting specific kinases like p38 or JAKs, which indirectly modulate these cascades (Schett et al., 2013). However, because these pathways are essential for normal immune surveillance, therapeutic inhibition carries risks of immunosuppression and increased susceptibility to infections (O'Shea et al., 2013).

Other names

NF-kappaB and MAPK signaling cascadePro-inflammatory signaling networkCytokine-mediated signal transductionNF-kB/MAPK pathway

Inhibition of upstream pro-inflammatory cytokines or their receptors, or the targeted inhibition of intracellular kinases (e.g., IKK, p38, JNK) to prevent the activation and nuclear translocation of pro-inflammatory transcription factors.