negative regulation of monocyte chemotactic protein-1 production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of production of monocyte chemotactic protein-1. [GOC:mah]

Negative regulation of monocyte chemotactic protein-1 (MCP-1) production is a complex biological process that involves multiple signaling pathways and regulatory mechanisms. MCP-1, also known as chemokine (C-C motif) ligand 2 (CCL2), is a potent chemokine that plays a crucial role in the recruitment and activation of monocytes and macrophages to sites of inflammation and tissue injury. Excessive or dysregulated production of MCP-1 has been implicated in various inflammatory and autoimmune diseases, including atherosclerosis, rheumatoid arthritis, and multiple sclerosis. Therefore, tightly regulating its production is essential for maintaining tissue homeostasis.

Several molecular mechanisms contribute to the negative regulation of MCP-1 production. These include:

1. **Transcriptional regulation:**
- **NF-κB inhibition:** Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a key transcription factor involved in MCP-1 gene expression. Several factors can inhibit NF-κB activation, including:
- **IκBα phosphorylation:** IκBα is an inhibitor of NF-κB. Phosphorylation of IκBα promotes its degradation, releasing NF-κB to translocate to the nucleus and activate MCP-1 gene transcription. Inhibiting IκBα phosphorylation can therefore reduce MCP-1 production.
- **Anti-inflammatory cytokines:** Cytokines such as IL-10 and TGF-β can suppress NF-κB activation and reduce MCP-1 expression.
- **Other transcription factor regulation:** In addition to NF-κB, other transcription factors, such as STAT3 and C/EBPβ, can also regulate MCP-1 gene expression. Targeting these factors could also contribute to negative regulation of MCP-1 production.

2. **Post-transcriptional regulation:**
- **mRNA stability:** MCP-1 mRNA stability can be regulated by various factors, including microRNAs. Specific microRNAs, such as miR-125b and miR-155, have been shown to target MCP-1 mRNA and reduce its stability, thereby decreasing MCP-1 production.
- **Translation inhibition:** Proteins such as tristetraprolin (TTP) can bind to MCP-1 mRNA and inhibit its translation into protein.

3. **Post-translational regulation:**
- **Protein degradation:** MCP-1 protein can be degraded by proteases such as matrix metalloproteinases (MMPs) and cathepsins. Increasing the activity of these proteases can reduce MCP-1 levels.

4. **Cell signaling pathways:**
- **PPARγ activation:** Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that can inhibit MCP-1 production by suppressing NF-κB activation and promoting the expression of anti-inflammatory genes.
- **SIRT1 activation:** Sirtuin 1 (SIRT1) is a deacetylase that can negatively regulate MCP-1 production by deacetylating and inactivating NF-κB.

5. **Other regulatory mechanisms:**
- **Cellular microenvironment:** Factors such as hypoxia, oxidative stress, and the presence of specific cell types can influence MCP-1 production.

The negative regulation of MCP-1 production is a complex and tightly controlled process that involves a multitude of molecular mechanisms. By understanding these mechanisms, researchers can identify potential targets for therapeutic interventions aimed at modulating MCP-1 levels and treating diseases associated with its dysregulation.'
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Proteins (2)

Compounds (54)