Inflammatory and stress-response signaling pathways

Inflammatory and stress-response signaling pathways are complex networks, including the Nuclear Factor-kappa B (NF-κB), Mitogen-Activated Protein Kinase (MAPK), and Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) cascades, that mediate cellular responses to environmental stressors and immunological triggers (Liu et al., 2017). These pathways function by transducing signals from cell-surface receptors to the nucleus, where they regulate the transcription of genes involved in inflammation, cell survival, and the immune response (Kyriakis & Avruch, 2012). Under normal conditions, these responses are tightly regulated to ensure host defense and tissue repair; however, chronic or aberrant activation is a primary driver of autoimmune diseases, chronic inflammation, and oncogenesis (Hu et al., 2021). Therapeutic targeting of these pathways has revolutionized the treatment of conditions like rheumatoid arthritis and psoriasis through the use of biologics and small-molecule inhibitors (NIH, 2023). Common drug classes include TNF-alpha antagonists, JAK inhibitors, and corticosteroids, which work by interrupting the signaling flow at various stages of the cascade (StatPearls, 2023). Despite their efficacy, these therapies carry significant risks, particularly regarding the suppression of the immune system, which can lead to opportunistic infections or impaired wound healing (PubMed, 2022). Monitoring biomarkers such as C-reactive protein and specific cytokine levels is often necessary to assess treatment efficacy and manage potential toxicity (NIH, 2023).

Other names

Stress-activated signaling pathwaysInflammatory cascadesPro-inflammatory signalingCellular stress responseStress-activated protein kinase (SAPK) pathways

Modulation of intracellular signaling through the inhibition of specific kinases (e.g., JAK, MAPK), antagonism of cytokine receptors (e.g., TNFR, IL-6R), or interference with transcription factor activation (e.g., NF-κB) to suppress pro-inflammatory gene expression.