Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19

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) transmembrane serine protease (TMPRSS2) keys to entry of SARS-CoV-2. We therefore hypothesized that air IPF may increase expression ACE2 TMPRSS2 in lung alveolar region. measured their levels tissues control non-IPF patients, used murine animal models study deterioration caused by particulate matter (PM) molecular pathways involved TMPRSS2. Results In cells expressing were limited human cells. largely upregulated co-expressed fibroblast specific protein 1 (FSP-1) + fibroblasts fibrotic tissue. models, PM increased severity bleomycin-induced fibrosis. also expressed FSP-1+ fibrosis, when combined with exposure, they further upregulated. The blocked deletion KC, homologue IL-8, or treatment reparixin, an inhibitor IL-8 receptors CXCR1/2. Conclusions These data suggested risk infection COVID-19 disease IPF. It can be mediated through upregulating fibroblasts, prevented blocking IL-8/CXCR1/2 pathway.