Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial cells.
In: Archives of Toxicology, Jg. 97 (2023-08-01), Heft 8, S. 2193-2208
Online
academicJournal
Zugriff:
Exposure to cigarettes and other nicotine-based products results in persistent inflammation in the lung. In recent years, electronic cigarettes (e-cigs) have become extremely popular among adults and youth alike. E-cigarette vapor-induced oxidative stress promotes protein breakdown, DNA damage and cell death, culminating in a variety of respiratory diseases. The proteasome, a multi-catalytic protease, superintends protein degradation within the cell. When cells are stimulated with inflammatory cytokines such as IFN-γ and TNF-α, the constitutive catalytic proteasome subunits are replaced by the inducible subunits-low-molecular mass polypeptide (LMP)2 (β1i), multi-catalytic endopeptidase complex-like (MECL)1 (β2i), and LMP7 (β5i), which are required for the production of certain MHC class I-restricted T-cell epitopes. In this study, we used human alveolar epithelial cells (A549) and exposed them to filtered air or (1%) tobacco-flavored (TF) electronic cigarette vapor condensate (ECVC) ± nicotine (6 mg/ml) (TF-ECVC ± N) for 24 h. We observed an increase in the levels of IFN-γ, TNF-α, and inducible proteasome subunits (LMP7/PSMB8, LMP2/PSMB9, MECL1/PSMB10), and a reduced expression of constitutive proteasome subunits (β1/PSMB6 and β2/PSMB7) in challenged A549 cells. Interestingly, knockdown of the inducible proteasome subunit LMP7 reversed ECVC-induced expression of NADPH oxidase and immunoproteasome subunits in A549 cells. In addition, pre-exposure to an LMP7 inhibitor (ONX-0914) abrogated the mRNA expression of several NOX subunits and rescued the excessive production/release of inflammatory cytokines/chemokines (IL-6, IL-8, CCL2, and CCL5) in ECVC-challenged cells. Our findings suggest an important role of LMP7 in regulating the expression of inflammatory mediators during ECVC exposure. Overall, our results provide evidence for proteasome-dependent ROS-mediated inflammation in ECVC-challenged cells. [ABSTRACT FROM AUTHOR]
Titel: |
Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial cells.
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Autor/in / Beteiligte Person: | Begum, R. ; Thota, S. ; Batra, S. |
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Zeitschrift: | Archives of Toxicology, Jg. 97 (2023-08-01), Heft 8, S. 2193-2208 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 0340-5761 (print) |
DOI: | 10.1007/s00204-023-03504-5 |
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