negative regulation of interleukin-1-mediated signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of interleukin-1-mediated signaling pathway. [GOC:obol]

Negative regulation of interleukin-1 (IL-1)-mediated signaling pathway is a crucial biological process that dampens the inflammatory response triggered by IL-1. IL-1 is a potent pro-inflammatory cytokine that plays a key role in the innate immune response to infection and injury. Upon binding to its receptor (IL-1R), IL-1 activates a signaling cascade that culminates in the activation of transcription factors, such as NF-κB, leading to the production of inflammatory mediators like TNF-α, IL-6, and chemokines.

This intricate pathway is tightly regulated by a network of inhibitory mechanisms to prevent excessive inflammation and tissue damage. Key regulatory components include:

* **IL-1 receptor antagonist (IL-1Ra):** IL-1Ra is a naturally occurring protein that competitively binds to IL-1R, preventing IL-1 from activating the signaling pathway.
* **Suppressor of cytokine signaling (SOCS) proteins:** SOCS proteins are induced by IL-1 signaling and act as negative feedback regulators by inhibiting the JAK-STAT pathway, a crucial component of IL-1 signaling.
* **A20:** A20 is a ubiquitin ligase that targets key signaling proteins in the IL-1 pathway for degradation, thereby attenuating signaling.
* **NF-κB inhibitors:** Several proteins, such as IκBα, inhibit NF-κB activation, thereby suppressing the transcription of inflammatory genes.
* **MicroRNAs:** MicroRNAs, small non-coding RNAs, can regulate the expression of key components in the IL-1 signaling pathway, contributing to its negative regulation.

These regulatory mechanisms work in concert to ensure that the IL-1 signaling pathway is appropriately activated only when needed and is subsequently shut down to prevent excessive inflammation. Disruption of these negative regulatory processes can contribute to chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and sepsis.'
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Proteins (2)

Compounds (4)