negative regulation of respiratory burst involved in inflammatory response

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency or extent of a phase of elevated metabolic activity, during which oxygen consumption increases made as a defense response ; this leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals. [GOC:BHF, GOC:dph, GOC:tb]

The negative regulation of respiratory burst is a crucial process in controlling inflammation. It involves a complex interplay of molecular mechanisms that dampen the excessive production of reactive oxygen species (ROS) by immune cells, primarily neutrophils and macrophages. These ROS, while essential for killing pathogens, can also cause significant damage to healthy tissues if left unchecked.

Here's a detailed description of the biological process:

1. **Signal Recognition and Initiation:**
- Inflammatory stimuli, such as pathogens, allergens, or tissue damage, trigger the activation of signaling pathways in immune cells.
- Key signaling molecules include Toll-like receptors (TLRs), cytokine receptors, and chemokine receptors.

2. **Activation of NADPH Oxidase:**
- Upon activation, the immune cell's NADPH oxidase complex, a key enzyme responsible for ROS generation, assembles and begins producing superoxide radicals (O2-) from molecular oxygen.
- This process involves the translocation of cytosolic components to the cell membrane, forming a functional oxidase.

3. **Negative Regulation Mechanisms:**
- **Antioxidant Enzymes:** Enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase neutralize ROS, converting them into less harmful molecules.
- **Redox-sensitive Transcription Factors:** Proteins like Nrf2 and NF-κB are sensitive to oxidative stress and regulate the expression of antioxidant genes, further mitigating ROS production.
- **Phosphatases:** Enzymes like PTEN and SHP-1 dephosphorylate key signaling proteins, suppressing the activation of NADPH oxidase and downstream pathways.
- **Cytokines and Signaling Molecules:** Anti-inflammatory cytokines, such as IL-10 and TGF-β, dampen the inflammatory response, reducing ROS production.
- **Apoptosis and Cell Death:** In some cases, excessive ROS can trigger programmed cell death (apoptosis), removing the source of ROS production.

4. **Resolution of Inflammation:**
- Effective negative regulation ensures a controlled inflammatory response, allowing for pathogen clearance and tissue repair without causing significant collateral damage.
- The balance between ROS production and negative regulation is crucial for maintaining immune homeostasis and preventing chronic inflammation.

This intricate process highlights the importance of negative regulation in preventing uncontrolled inflammation, thereby contributing to the body's overall health and well-being.'
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Proteins (1)

Compounds (2)