Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial...

Area of Science:

• Pulmonary toxicology
• Cellular immunology
• Molecular biology

Background:

• Electronic cigarettes (e-cigs) are increasingly popular, and their vapor can cause lung inflammation and oxidative stress.
• The proteasome, a protein-degrading complex, has inducible subunits (immunoproteasome) crucial for immune responses.
• Inflammatory cytokines like IFN-γ and TNF-α can upregulate immunoproteasome subunits.

Purpose of the Study:

• To investigate the role of proteasome subunits, specifically LMP7, in electronic cigarette vapor condensate (ECVC)-induced inflammation in human alveolar epithelial cells (A549).
• To explore the relationship between ECVC exposure, oxidative stress, and the expression of proteasome subunits and inflammatory mediators.

Main Methods:

• A549 cells were exposed to filtered air or tobacco-flavored ECVC with or without nicotine.
• Analyzed levels of inflammatory cytokines (IFN-γ, TNF-α) and proteasome subunits (constitutive and inducible).
• Utilized gene knockdown of LMP7 and an LMP7 inhibitor (ONX-0914) to assess their impact on ECVC-induced changes.

Main Results:

• ECVC exposure increased IFN-γ, TNF-α, and inducible proteasome subunits (LMP7, LMP2, MECL1) while decreasing constitutive subunits.
• LMP7 knockdown reversed ECVC-induced NADPH oxidase and immunoproteasome subunit expression.
• LMP7 inhibition reduced NOX subunit mRNA and inflammatory cytokine/chemokine release (IL-6, IL-8, CCL2, CCL5).

Conclusions:

• LMP7 plays a significant role in regulating inflammatory mediator expression during ECVC exposure.
• Findings support a model of proteasome-dependent, reactive oxygen species (ROS)-mediated inflammation in ECVC-challenged cells.
• Targeting LMP7 may offer a therapeutic strategy for e-cigarette-induced lung inflammation.