Mitogen-activated protein kinase signaling and nuclear factor-kappa B pathway (MAPK and NF-κB pathways)

The Mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways are fundamental signaling cascades that regulate cellular responses to environmental stress and inflammatory cytokines within the intestinal mucosa (Source: PubMed: 28839420). The MAPK family, comprising p38, JNK, and ERK, mediates signal transduction that influences cell proliferation, differentiation, and apoptosis in the gut epithelium (Source: UniProt: P31749, P45983). Concurrently, the NF-κB pathway serves as a central regulator of the innate and adaptive immune response, where its activation leads to the transcription of various pro-inflammatory mediators (Source: UniProt: P19838). In patients with inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, these pathways are often chronically activated, leading to sustained mucosal inflammation and tissue damage (Source: NIH: NBK532264). While these pathways are not single molecular targets, they contain numerous druggable enzymes like IκB kinase (IKK) and p38 MAPK that are investigated for their therapeutic potential (Source: PubMed: 30107161). Therapeutic modulation of these pathways aims to suppress the overproduction of cytokines like TNF-α and IL-1β to restore intestinal barrier function and promote mucosal healing (Source: PubMed: 25183969).

Other names

MAPK/NF-κB signaling axis (Source: PubMed: 28839420)Inflammatory signaling pathways in the gut (Source: NIH: NBK532264)Intestinal inflammatory signaling (Source: PubMed: 30107161)

Inhibition of phosphorylation cascades within the MAPK family (p38, JNK, ERK) and inhibition of the IκB kinase (IKK) complex to prevent the nuclear translocation of NF-κB transcription factors (Source: PubMed: 28839420, 30107161).