Page last updated: 2024-10-24

negative regulation of macrophage inflammatory protein 1 alpha production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of production of macrophage inflammatory protein 1 alpha. [GOC:mah]

Negative regulation of macrophage inflammatory protein 1 alpha (MIP-1α) production is a crucial process in dampening inflammation and preventing excessive immune responses. MIP-1α, a potent chemokine, plays a key role in attracting and activating immune cells, particularly monocytes and macrophages, to sites of inflammation. Excessive production of MIP-1α can lead to chronic inflammation and tissue damage.

The negative regulation of MIP-1α production involves a complex interplay of signaling pathways and regulatory molecules, including:

**1. Transcriptional Regulation:**
* **Nuclear factor kappa B (NF-κB):** NF-κB is a master regulator of inflammation. Upon activation by pro-inflammatory stimuli, NF-κB translocates to the nucleus and promotes transcription of inflammatory genes, including MIP-1α. Negative regulation occurs through:
* **Inhibition of NF-κB activation:** Several pathways can inhibit NF-κB activation, such as the activation of IκBα, a protein that sequesters NF-κB in the cytoplasm, preventing its nuclear translocation.
* **Induction of NF-κB inhibitors:** Molecules like IκBζ and A20 can directly inhibit NF-κB activity.
* **Other transcription factors:** Other transcription factors, including STATs (signal transducer and activator of transcription), AP-1 (activator protein 1), and C/EBP (CCAAT/enhancer-binding protein), can also regulate MIP-1α expression, and their activity can be modulated by various signaling pathways.

**2. Post-transcriptional Regulation:**
* **MicroRNAs (miRNAs):** miRNAs are small non-coding RNAs that regulate gene expression by binding to target mRNAs, leading to their degradation or translational repression. Specific miRNAs have been shown to target MIP-1α mRNA, reducing its translation into protein.
* **RNA-binding proteins:** Certain RNA-binding proteins can regulate MIP-1α mRNA stability and translation.

**3. Post-translational Regulation:**
* **Protein degradation:** MIP-1α protein can be targeted for degradation by proteasomes or lysosomes, reducing its levels in the cell.
* **Protein modifications:** Modifications like phosphorylation or ubiquitination can alter MIP-1α activity or stability.

**4. Receptor Antagonism:**
* **Soluble receptors:** Soluble forms of MIP-1α receptors, CCR1 and CCR5, can act as decoys, binding to MIP-1α and preventing it from interacting with its cognate receptors on target cells.

**5. Immune Cell Regulation:**
* **Regulatory T cells (Tregs):** Tregs suppress inflammatory responses, including MIP-1α production, by releasing anti-inflammatory cytokines like IL-10.
* **Other immune cells:** Macrophages themselves can produce anti-inflammatory cytokines, such as IL-10 and TGF-β, which can suppress MIP-1α production by other macrophages.

**6. Environmental Factors:**
* **Anti-inflammatory agents:** Drugs like corticosteroids or NSAIDs can inhibit NF-κB activation, reducing MIP-1α production.
* **Diet and lifestyle:** Dietary factors and exercise can influence inflammation and potentially modulate MIP-1α expression.

The negative regulation of MIP-1α production is a complex and tightly controlled process, involving multiple cellular mechanisms and signaling pathways. Its dysregulation can contribute to a variety of inflammatory diseases. Understanding these regulatory mechanisms is essential for developing therapeutic strategies to control inflammation and improve patient outcomes.'
"

Proteins (1)

ProteinDefinitionTaxonomy
Arginase-2, mitochondrialAn arginase-2, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P78540]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
n(omega)-hydroxyarginineN(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-arginineL-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