negative regulation of chemokine (C-C motif) ligand 4 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 4. [GOC:mah]
Negative regulation of chemokine (C-C motif) ligand 4 production is a complex process that involves various molecular mechanisms to control the levels of this inflammatory mediator. CCL4, also known as macrophage inflammatory protein-1β (MIP-1β), is a potent chemokine that plays a crucial role in recruiting immune cells to sites of inflammation. Excessive CCL4 production can contribute to the development of chronic inflammatory diseases, making its tight regulation essential for maintaining tissue homeostasis.
Several key regulatory mechanisms are involved in the negative regulation of CCL4 production, including:
* **Transcriptional regulation:** The expression of CCL4 is tightly regulated at the transcriptional level. Transcription factors such as NF-κB, AP-1, and STAT1 can induce CCL4 gene expression in response to inflammatory stimuli. However, negative regulatory mechanisms can suppress CCL4 transcription. For example, anti-inflammatory cytokines like IL-10 can inhibit NF-κB activation, thereby reducing CCL4 production.
* **Post-transcriptional regulation:** MicroRNAs (miRNAs) can target the CCL4 mRNA and promote its degradation, leading to reduced CCL4 production. Specific miRNAs have been shown to suppress CCL4 expression in various cell types.
* **Post-translational regulation:** CCL4 can be regulated at the post-translational level by proteolytic degradation. Proteases such as MMP-9 can cleave CCL4, rendering it inactive. Additionally, glycosylation and phosphorylation can influence CCL4 stability and its ability to bind to its receptor.
* **Receptor signaling:** CCL4 exerts its effects by binding to its receptor CCR5. Downregulation of CCR5 expression can reduce the sensitivity of cells to CCL4, thereby limiting its inflammatory effects.
The specific mechanisms involved in the negative regulation of CCL4 production can vary depending on the cell type, the inflammatory stimulus, and the context. However, the overall goal of these regulatory processes is to maintain appropriate levels of CCL4 and prevent excessive inflammation. Dysregulation of CCL4 production has been implicated in various diseases, including autoimmune disorders, cancer, and chronic inflammatory diseases. Understanding the complex mechanisms involved in CCL4 regulation is crucial for developing therapeutic strategies that target this pathway to modulate inflammation and treat disease.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Arginase-2, mitochondrial | An arginase-2, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P78540] | Homo sapiens (human) |
Compounds (4)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| n(omega)-hydroxyarginine | N(5)-[(Z)-amino(hydroxyimino)methyl]-L-ornithine : An N(5)-[amino(hydroxyimino)methyl]-L-ornithine in which the double bond has Z-configuration. N(omega)-hydroxyarginine: can cause vasorelaxation of bovine intrapulmonary artery; structure given in first source | amino acid zwitterion; N(5)-[(E)-amino(hydroxyimino)methyl]ornithine; N(5)-[(hydroxyamino)(imino)methyl]ornithine; N(5)-[(Z)-amino(hydroxyimino)methyl]ornithine; N(5)-[amino(hydroxyimino)methyl]-L-ornithine; N(5)-[amino(hydroxyimino)methyl]ornithine; N(omega)-hydroxy-L-arginine | |
| Nomega-hydroxy-nor-l-arginine | L-alpha-amino acid | ||
| (S)-2-amino-6-boronohexanoic acid | (S)-2-amino-6-boronohexanoic acid : L-Norleucine substituted at C-6 with a borono group. | non-proteinogenic L-alpha-amino acid; organoboron compound | |
| 2-amino-6-boronohexanoic acid |