In UC, the activity of pro- and anti-inflammatory mediators is dysregulated, provoking an exaggerated immune response and initiating a chronic inflammatory cycle.1-3
Proinflammatory mediators, such as TNF-a and IL-13, recruit immune cells to sites of inflammation through intracellular signalling pathways. These pathways include the JAK-STAT, MAPK, and NF-kB pathways.4,5
Dysregulation of JAK-STAT, MAPK, or NF-kB activity is associated with inflammatory cytokine secretion through transcription factors. Excessive inflammatory cytokine production can lead to tissue damage, haemodynamic changes, and ultimately organ failure.4
IL, interleukin; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; STAT, signal transducer and activator of transcription; TNF, tumour necrosis factor; UC, ulcerative colitis.
REFERENCES: 1. Coskun M, Salem M, Pedersen J, Nielsen OH. Pharmacol Res. 2013;76:1-8. 2. Fernández-Clotet A, Castro-Poceiro J, Panés J. Curr Pharm Des. 2019;25(1):32-40. 3. Neurath MF. Nat Rev Immunol. 2014;14(5):329-342. 4. Chen L, Deng H, Cui H, et al. Oncotarget. 2017;9(6):7204-7218. 5. Pedersen J, Coskun M, Soendergaard C, Salem M, Nielsen OH. World J Gastroenterol. 2014;20(1):64-77.