Proinflammatory cytokine signaling downstream of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK)

Proinflammatory cytokine signaling downstream of NF-κB and MAPK is a fundamental signaling axis that translates extracellular stress and inflammatory stimuli into a coordinated cellular response. The Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways, including p38, JNK, and ERK, are activated by receptors such as Toll-like receptors (TLRs) and Tumor Necrosis Factor receptors (TNFRs) (Liu et al., 2017). Once activated, these pathways converge on the nucleus to induce the transcription of genes encoding various proinflammatory cytokines, chemokines, and adhesion molecules (Zhang & Cao, 2019). This signaling cascade is a primary driver of the inflammatory response in diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. While the entire signaling network is not a single therapeutic target, its individual components—such as TNF-α, IL-6, and various upstream kinases—are the focus of numerous blockbuster drugs (Kaminska, 2005). Therapeutic strategies include the use of monoclonal antibodies to neutralize cytokines or small molecules to inhibit specific intracellular kinases within the pathway.

Other names

NF-kappaB and MAPK inflammatory cascadePro-inflammatory signaling pathwaysCytokine storm signalingNF-κB/MAPK-mediated cytokine production

Inhibition of signal transduction through the blockade of upstream kinases (e.g., IKK, JAK, MEK), neutralization of secreted proinflammatory cytokines, or antagonism of cytokine receptors to prevent downstream transcriptional activation.