Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox

Area of Science:

• Immunology
• Molecular Biology
• Biochemistry

Background:

• Immune responses are triggered by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
• DAMPs are typically intracellular proteins released upon cell damage or death.
• Extracellular conditions can alter DAMP structure and function, potentially leading to inflammation.

Purpose of the Study:

• To discuss the consequences of DAMP oxidation on acute inflammation.
• To explore how DAMPs might evade oxidation and promote pathology.
• To propose a role for DAMPs and redox environment in chronic inflammatory diseases.

Main Methods:

• Literature review and theoretical discussion.
• Analysis of molecular mechanisms of DAMP release and function.
• Exploration of redox biology in the context of inflammation.

Main Results:

• DAMP oxidation outside the cell can lead to functional denaturation.
• DAMPs may adopt conformations or alter the extracellular redox environment to avoid inactivation.
• Oxidized DAMPs can promote acute and chronic inflammation, including autoimmunity, viral infections, and cancer.

Conclusions:

• DAMP oxidation significantly impacts the outcome of acute inflammation.
• Persistent DAMP release and function, coupled with a disordered redox environment, likely mediate chronic inflammatory conditions.
• Targeting DAMPs and redox balance may offer therapeutic strategies for inflammatory diseases.