cellular response to interleukin-6

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-6 stimulus. [GOC:mah]

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a critical role in a wide range of biological processes, including immune responses, inflammation, and hematopoiesis. Upon binding to its receptor, IL-6 initiates a signaling cascade that ultimately leads to the activation of various transcription factors, including STAT3. This activation results in the expression of a diverse array of genes involved in cellular response to IL-6. The process can be broadly categorized into the following stages:

1. **Ligand Binding and Receptor Activation:** IL-6 binds to its receptor, a heterodimer composed of the IL-6 receptor α-chain (IL-6Rα) and the glycoprotein 130 (gp130) transmembrane protein. This binding event triggers the dimerization of gp130, bringing together the intracellular domains of the receptor complex.

2. **Signal Transduction:** The dimerized gp130 recruits Janus kinase (JAK) family members, specifically JAK1 and JAK2. These kinases phosphorylate each other and subsequently phosphorylate tyrosine residues within the cytoplasmic tails of gp130. These phosphorylated tyrosines serve as docking sites for the signal transducer and activator of transcription 3 (STAT3).

3. **STAT3 Activation and Nuclear Translocation:** STAT3 binds to the phosphorylated tyrosine residues on gp130. This binding event triggers the phosphorylation of STAT3 by JAK kinases, leading to its dimerization. The activated STAT3 dimers translocate from the cytoplasm to the nucleus.

4. **Gene Regulation:** In the nucleus, activated STAT3 dimers bind to specific DNA sequences known as STAT3 response elements (SREs) in the promoter regions of target genes. This binding event initiates transcription of genes involved in a wide range of cellular responses to IL-6.

5. **Cellular Responses:** The expression of IL-6-responsive genes leads to a diverse array of cellular responses, including:
- **Inflammation:** IL-6 promotes the production of pro-inflammatory cytokines like TNF-α and IL-1β, contributing to inflammation.
- **Immune Responses:** IL-6 plays a key role in adaptive immune responses by promoting antibody production by B cells and differentiation of T helper cells.
- **Hematopoiesis:** IL-6 regulates the production of blood cells, particularly neutrophils and platelets.
- **Acute Phase Response:** IL-6 stimulates the liver to produce acute phase proteins, such as C-reactive protein, during inflammation.
- **Cell Proliferation and Differentiation:** IL-6 can promote cell proliferation and differentiation in various cell types, including hepatocytes and muscle cells.
- **Metabolic Regulation:** IL-6 has been implicated in metabolic regulation, influencing glucose metabolism and insulin sensitivity.

6. **Negative Feedback Regulation:** To prevent excessive signaling, negative feedback mechanisms are in place. These mechanisms include:
- **Protein tyrosine phosphatases (PTPs):** PTPs dephosphorylate STAT3, inactivating it.
- **Suppressor of cytokine signaling (SOCS) proteins:** SOCS proteins bind to JAK kinases, inhibiting their activity.
- **Ubiquitination and proteasomal degradation:** STAT3 can be ubiquitinated and degraded by the proteasome, limiting its signaling activity.

In summary, IL-6 signaling is a complex and highly regulated process that involves multiple signaling pathways and transcription factors. The activation of STAT3 plays a central role in mediating the diverse cellular responses to IL-6, contributing to a wide range of physiological and pathological processes.'
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Proteins (4)

Compounds (90)