Low-grade inflammatory polarization of monocytes impairs wound healing

Area of Science:

• Immunology
• Cell Biology
• Wound Healing Research

Background:

• Impaired wound healing is linked to low-grade inflammation and persistent subclinical endotoxin.
• Chronic inflammation can lead to monocyte polarization, hindering effective wound repair.
• Mechanisms underlying monocyte polarization by low-dose endotoxin remain unclear.

Purpose of the Study:

• To investigate how sustained exposure to super-low-dose endotoxin influences monocyte polarization.
• To elucidate the cellular mechanisms driving endotoxin-induced monocyte polarization.
• To identify potential therapeutic strategies for endotoxin-mediated impaired wound healing.

Main Methods:

• In vitro and in vivo studies using super-low-dose endotoxin.
• Flow cytometry to analyze monocyte populations (CD11b(+) Ly6C(high)) and CCR5 expression.
• Assessment of cellular stress markers and lysosome function.
• Evaluation of the transcription factor IRF5.
• Treatment with Tauroursodeoxycholic acid (TUDCA) in a mouse wound healing model.

Main Results:

• Super-low-dose endotoxin induced a low-grade inflammatory monocyte state in vitro and in vivo.
• Elevated CD11b(+) Ly6C(high) monocytes and sustained CCR5 expression were observed.
• Endotoxin exposure led to cellular stress, altered lysosome function, and increased IRF5.
• TUDCA treatment inhibited monocyte polarization and accelerated wound healing in mice.

Conclusions:

• Sustained endotoxin challenge drives low-grade inflammatory monocyte polarization via cellular stress and IRF5.
• TUDCA effectively counteracts endotoxin-induced monocyte polarization and enhances wound repair.
• This study reveals key mechanisms and a potential therapeutic target for endotoxin-related healing deficits.