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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 29, 2023 |
| Title |
Lung emphysema can be elicited by nanoparticle triggered, p38 MAPK mediated virus reactivation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Environmental particle inhalation and persistent herpesvirus infection are omnipresent and associated with chronic lung diseases. Previously, we showed that pulmonary exposure to soot-like carbonaceous nanoparticles (CNP) or fibre-shaped engineered double-walled carbon nanotubes (DWCNT) induced an increase of lytic virus protein expression in latently murine gammaherpesvirus 68 (MHV-68) infected mouse lungs, with a similar pattern as acute infection suggesting virus reactivation. However, the molecular mechanisms underlying herpesvirus reactivation as well as herpesvirus reactivation associated disease exacerbation caused by particle exposure remain unclear. Here, we investigated the effects of environmental relevant repeated particle exposure and herpesvirus reactivation mechanistically, and therapeutically. In the MHV-68 mouse model, we identified elevated lung inflammation and emphysema-like injury after repetitive CNP exposure. We further uncovered that CNP reactivated latent herpesvirus mainly in CD11b+ macrophages. Mechanistically, ERK1/2, JNK and p38 MAPK were rapidly activated after CNP and DWCNT exposure in persistently MHV-68 infected bone marrow-derived macrophages, followed by upregulation of viral gene expression and increased viral titer but without generating a pro-inflammatory transcriptional signature. Pharmacological inhibition of p38 activation abrogated CNP but not DWCNT triggered virus reactivation. In vivo, p38 inhibitor pretreatment of latently infected mice also attenuated CNP exposure induced MHV-68 reactivation. Our findings suggest that particle pollution is an environmental challenge to trigger herpesvirus reactivation and related chronic lung disease by activating latent herpesvirus via p38 MAPK dependent signalling. Pharmacological p38 inhibition might serve as a protective target to alleviate particle exposure related chronic lung disease exacerbations.
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| Overall design |
Ana-1/MHV-68 cells were exposed to CNP, DWCNT, LPS or controls
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| Contributor(s) |
Han L, Haefner V, Yu Y, Han B, Ren H, Irmler M, Beckers J, Feuchtinger A, Yildrim AO, Adler H, Stoeger T |
| Citation(s) |
37856828 |
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| Submission date |
Jan 26, 2023 |
| Last update date |
Nov 14, 2023 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (64)
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| GSM6997259 |
CNP_3h_Ana-1_infected_with_MHV-68 _rep1 |
| GSM6997260 |
CNP_3h_Ana-1_infected_with_MHV-68 _rep2 |
| GSM6997261 |
CNP_3h_Ana-1_infected_with_MHV-68 _rep3 |
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| Relations |
| BioProject |
PRJNA928453 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223818_RAW.tar |
76.0 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE223818_matrix_and_p-values.txt.gz |
6.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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