Macrophage HDAC10 deficiency ameliorates PM2.5-induced lung inflammation by suppressing Beclin1...

Area of Science:

• Environmental Health
• Cellular Biology
• Immunology

Background:

• Fine particulate matter (PM2.5) is a major environmental risk factor for pulmonary inflammation.
• The cellular mechanisms driving PM2.5-induced lung inflammation are not fully understood.

Purpose of the Study:

• To identify key regulators of PM2.5-induced airway inflammation in macrophages.
• To elucidate the role of histone deacetylase 10 (HDAC10) in PM2.5-mediated pulmonary responses.

Main Methods:

• Investigated HDAC10 expression in lung macrophages following PM2.5 exposure in vivo and in vitro.
• Utilized myeloid-specific Hdac10 knockout mice to assess its role in inflammation.
• Examined the interaction between HDAC10 and Beclin1, focusing on Beclin1 deacetylation at K5.
• Evaluated the effects of pharmacological HDAC10 inhibition (salvianolic acid B) on inflammation and autophagy.
• Analyzed HDAC10 and Beclin1 acetylation in lung tissues from chronic obstructive pulmonary disease (COPD) patients.

Main Results:

• PM2.5 exposure increased HDAC10 expression in lung macrophages.
• Deletion of Hdac10 in myeloid cells significantly reduced PM2.5-induced airway inflammation and inflammatory cytokine production by inhibiting macrophage autophagy.
• HDAC10 directly deacetylated Beclin1 at K5, a critical step for autophagic flux and inflammation.
• Pharmacological inhibition of HDAC10 ameliorated PM2.5-induced lung inflammation.
• COPD patients exhibited elevated HDAC10 expression and reduced Beclin1 acetylation, correlating with inflammation severity.

Conclusions:

• HDAC10 acts as a critical regulator of PM2.5-induced pulmonary inflammation by controlling macrophage autophagy.
• The HDAC10-Beclin1 axis is a novel pathway linking PM2.5 exposure to macrophage autophagy and lung inflammation.
• Targeting HDAC10 presents a potential therapeutic strategy for managing PM2.5-related respiratory diseases like COPD.