Macrophage-derived sulfur dioxide is a novel inflammation regulator

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Research

Background:

• Macrophage-driven inflammation is central to cardiovascular diseases.
• Mechanisms controlling macrophage inflammatory responses remain incompletely understood.

Purpose of the Study:

• To investigate the role of endogenous sulfur dioxide (SO2) in regulating macrophage activation and inflammation.
• To identify the enzyme responsible for SO2 production in macrophages.

Main Methods:

• Utilized High-Performance Liquid Chromatography (HPLC) and SO2-specific fluorescent probes to detect endogenous SO2 production in RAW267.4 macrophages.
• Investigated the expression and function of aspartate aminotransferase (AAT) in macrophages.
• Employed AAT2 knockdown and SO2 donor treatments to assess effects on inflammatory markers (TNF-α, IL-6) and NF-κB signaling.
• Evaluated macrophage infiltration in a mouse model of Angiotensin II (AngII)-induced cardiovascular disease.

Main Results:

• Demonstrated endogenous SO2 production in RAW267.4 macrophages, identifying aspartate aminotransferase (AAT) as the SO2-generating enzyme.
• AAT2 knockdown led to spontaneous macrophage inflammation (increased TNF-α, IL-6, chemotaxis) and NF-κB pathway activation.
• SO2 supplementation reversed inflammation and NF-κB activation caused by AAT2 knockdown.
• SO2 donors attenuated AngII-induced macrophage inflammation and infiltration in mouse hearts.

Conclusions:

• Macrophage-derived SO2 acts as a crucial endogenous regulator of macrophage activation.
• SO2 functions as an intrinsic
• on-off switch
• controlling macrophage inflammatory states.
• This discovery provides a novel therapeutic target for managing cardiovascular diseases through modulation of macrophage SO2 signaling.