Nuclear Alarmin Cytokines in Inflammation.

Area of Science:

• Immunology
• Cell Biology

Background:

• Pathogen-associated molecular patterns (PAMPs) trigger innate immunity via pattern recognition receptors (PRRs).
• Cellular stress releases endogenous damage-associated molecular patterns (DAMPs), also known as alarmins, which bind PRRs, inducing sterile inflammation.
• Alarmins can also promote tissue repair and exhibit dual nuclear and extracellular functions.

Purpose of the Study:

• To review the role of nuclear alarmins, including high-mobility group box-1 protein (HMGB1), interleukin (IL)-33, and IL-1α, in physiological and stress conditions.
• To propose a novel function of these alarmins as key initiators of sterile inflammation.

Main Methods:

• Literature review of studies on alarmins and sterile inflammation.
• Analysis of the molecular mechanisms underlying alarmin-mediated inflammation.
• Synthesis of current knowledge on HMGB1, IL-33, and IL-1α in cellular stress responses.

Main Results:

• Nuclear alarmins HMGB1, IL-33, and IL-1α are implicated in sterile inflammation.
• These molecules are released under physiological stress and cellular damage.
• Alarmins contribute to both inflammatory and tissue repair processes.

Conclusions:

• Nuclear alarmins are central initiators of sterile inflammation.
• Understanding alarmin function is crucial for developing therapies for inflammatory diseases.
• Further research is needed to fully elucidate the dual roles of alarmins in health and disease.