Nuclear factor kappa-light-chain-enhancer of activated B cells and p38 mitogen-activated protein kinase signaling pathway (NF-κB / p38 MAPK pathway)

The NF-κB and p38 MAPK signaling pathways are fundamental intracellular cascades that coordinate the inflammatory response in intestinal and immune cells [1]. NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) acts as a master transcription factor that translocates to the nucleus upon activation to induce the expression of pro-inflammatory cytokines, chemokines, and anti-apoptotic genes [2]. Concurrently, p38 MAPK (mitogen-activated protein kinase) is a stress-activated kinase that regulates the production of inflammatory mediators and modulates cellular responses to environmental stress and cytokines [3]. In the context of intestinal health, dysregulation of these pathways is strongly associated with inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, where excessive signaling leads to chronic mucosal inflammation and tissue destruction [4]. Pharmacological targeting of these pathways involves the use of small molecule inhibitors or biologics to dampen the immune response, although systemic inhibition is often limited by safety concerns such as immunosuppression and hepatotoxicity [5]. These pathways also play a role in the progression of colorectal cancer by promoting cell survival and an inflammatory microenvironment [6].

Other names

NF-kappaB/p38 MAPK axisNF-kB/p38 signaling pathwayPro-inflammatory signaling cascade

Inhibition of p38 MAPK phosphorylation or inhibition of NF-κB nuclear translocation to suppress the production of pro-inflammatory mediators [3, 5].