Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19.
Part Fibre Toxicol
; 18(1): 11, 2021 03 11.
Article
in English
| MEDLINE | ID: covidwho-1133602
ABSTRACT
BACKGROUND:
Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.RESULTS:
In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.CONCLUSIONS:
These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Serine Endopeptidases
/
Particulate Matter
/
Idiopathic Pulmonary Fibrosis
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Part Fibre Toxicol
Journal subject:
Toxicology
Year:
2021
Document Type:
Article
Affiliation country:
S12989-021-00404-3
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