negative regulation of chemokine (C-C motif) ligand 5 production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of production of chemokine (C-C motif) ligand 5. [GOC:mah]

Negative regulation of chemokine (C-C motif) ligand 5 production involves a complex interplay of molecular mechanisms that aim to dampen the production of CCL5, a key chemokine involved in attracting immune cells to sites of inflammation and infection. Here's a detailed breakdown:

1. **Transcriptional Regulation:**
- **Suppression of CCL5 gene transcription:**
- **Transcription factors:** Various transcription factors, including NF-κB, AP-1, and STATs, can bind to regulatory elements in the CCL5 gene promoter to activate its transcription. Conversely, other factors like C/EBPβ, Egr-1, and HIF-1α can suppress transcription.
- **Epigenetic modifications:** Modifications like methylation of the CCL5 gene promoter can silence transcription.
- **MicroRNAs (miRNAs):** miRNAs are small non-coding RNAs that regulate gene expression. Specific miRNAs, such as miR-125b and miR-146a, have been shown to target CCL5 mRNA and reduce its translation.

2. **Post-transcriptional Regulation:**
- **mRNA stability:** CCL5 mRNA stability can be regulated by factors that influence its degradation, such as AU-rich elements (AREs) in its 3' untranslated region (UTR). These AREs interact with RNA-binding proteins that can either stabilize or destabilize the mRNA.
- **mRNA translation:** Factors affecting the translation of CCL5 mRNA can also regulate its production. For example, specific proteins might bind to CCL5 mRNA and inhibit its translation.

3. **Post-translational Regulation:**
- **Protein stability:** CCL5 protein can be degraded by proteases like cathepsin G and matrix metalloproteinases.
- **Protein trafficking:** CCL5 is secreted from cells, and its secretion can be modulated by factors that affect its trafficking within the cell.

4. **Cellular Interactions:**
- **Cell-cell communication:** Cells can communicate with each other through paracrine or autocrine signaling pathways that involve chemokine receptors and ligands. These interactions can modulate CCL5 production.
- **Immune cell modulation:** Certain immune cells, like T regulatory cells (Tregs), can produce factors that suppress CCL5 production in other cells.

5. **Pharmacological Interventions:**
- **Drugs:** Some drugs, such as corticosteroids and anti-inflammatory agents, can reduce CCL5 production by targeting various regulatory pathways involved in its production.

In summary, negative regulation of CCL5 production involves intricate mechanisms at multiple levels, aiming to control the recruitment of immune cells and maintain immune homeostasis. Understanding these regulatory processes is crucial for developing therapies that target CCL5 production in various diseases, including inflammatory disorders, autoimmune diseases, and cancer.'
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Proteins (2)

Compounds (5)