Intracellular inflammatory signaling pathways

Intracellular inflammatory signaling pathways represent a broad category of biochemical cascades that transmit signals from the cell surface to the nucleus to initiate an inflammatory response. These pathways, including the Nuclear Factor-kappa B (NF-κB), Mitogen-Activated Protein Kinase (MAPK), and Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) systems, are activated by various stimuli such as cytokines, growth factors, and microbial components (StatPearls, 2023). Once triggered, these cascades lead to the phosphorylation and activation of transcription factors that upregulate the expression of pro-inflammatory genes (Nature Reviews Drug Discovery, 2021). Chronic or aberrant activation of these pathways is central to the pathogenesis of autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease, and certain malignancies (PubMed, 2022). Pharmacological targeting of specific nodes within these pathways, particularly through small-molecule kinase inhibitors, has become a cornerstone of modern anti-inflammatory therapy (NIH, 2023). However, because these pathways also govern essential homeostatic functions, therapeutic modulation carries risks of systemic immunosuppression and other off-target effects.

Other names

Pro-inflammatory signaling cascadesInflammatory signal transduction pathwaysCytokine signaling pathwaysIntracellular inflammatory cascades

Inhibition of intracellular kinases such as Janus kinases (JAKs) or Mitogen-activated protein kinases (MAPKs), blockade of transcription factor activation (e.g., NF-κB), or modulation of the proteasome to prevent degradation of inhibitory proteins like IκB.