Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

被引:20
作者
Albini, Adriana [1 ]
Calabrone, Luana [1 ]
Carlini, Valentina [2 ]
Benedetto, Nadia [1 ]
Lombardo, Michele [3 ]
Bruno, Antonino [4 ]
Noonan, Douglas M. [2 ,5 ]
机构
[1] Ist Ricovero & Cura Carallere Sci IRCCS MulliMed, Lab Vasc Biol & Angiogenesis, Milan, Italy
[2] IRCCS MultiMed, Unit Mol Pathol Biochem & Immunol, Milan, Italy
[3] IRCCS MultiMed, Dept Cardiol, Milan, Italy
[4] IRCCS MultiMed, Lab Innate Immun, Unit Mol Pathol Biochem & Immunol, Milan, Italy
[5] Univ Insubria, Dept Biotechnol & Life Sci, Immunol & Gen Pathol Lab, Varese, Italy
关键词
ACE2; IL-10; COVID-19 pro-inflammatory cytokines; SARS-COV-2; cytokine storm; metformin; sartans; ARDS; PULMONARY ARTERIAL-HYPERTENSION; RESPIRATORY SYNDROME SARS; ENZYME; ACE2; CYTOKINE/CHEMOKINE PROFILES; IMMUNE-RESPONSES; INTERLEUKIN-10; IL-10; CORONAVIRUS; CYTOKINES; COVID-19;
D O I
10.3389/fimmu.2021.718136
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a "cytokine storm" upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intestinal, and endothelial cells. High ACE2 levels protect from inflammation. Despite the relevance of ACE2 levels in COVID-19 pathogenesis, experimental studies to comprehensively address the question of ACE2 regulations are still limited. A relevant observation from the clinic is that, besides the pro-inflammatory cytokines, such as IL-6 and IL-1 beta, the anti-inflammatory cytokine IL-10 is also elevated in worse prognosis patients. This could represent somehow a "danger signal", an alarmin from the host organism, given the immuno-regulatory properties of the cytokine. Here, we investigated whether IL-10 could increase ACE2 expression in the lung-derived Calu-3 cell line. We provided preliminary evidence of ACE2 mRNA increase in cells of lung origin in vitro, following IL-10 treatment. Endothelial cell infection by SARS-COV-2 is associated with vasculitis, thromboembolism, and disseminated intravascular coagulation. We confirmed ACE2 expression enhancement by IL-10 treatment also on endothelial cells. The sartans (olmesartan and losartan) showed non-statistically significant ACE2 modulation in Calu-3 and endothelial cells, as compared to untreated control cells. We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells. We hypothesized that IL-10 could be a danger signal, and its elevation could possibly represent a feedback mechanism fighting inflammation. Although further confirmatory studies are required, inducing IL-10 upregulation could be clinically relevant in COVID-19-associated acute respiratory distress syndrome (ARDS) and vasculitis, by reinforcing ACE2 levels.
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页数:10
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共 63 条
[1]   The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies [J].
Albini, Adriana ;
Di Guardo, Giovanni ;
Noonan, Douglas McClain ;
Lombardo, Michele .
INTERNAL AND EMERGENCY MEDICINE, 2020, 15 (05) :759-766
[2]   Genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus [J].
Baas, Tracey ;
Roberts, Anjeanette ;
Teal, Thomas H. ;
Vogel, Leatrice ;
Chen, Jun ;
Tumpey, Terrence M. ;
Katze, Michael G. ;
Subbarao, Kanta .
JOURNAL OF VIROLOGY, 2008, 82 (19) :9465-9476
[3]   Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis [J].
Bramante, Carolyn T. ;
Ingraham, Nicholas E. ;
Murray, Thomas A. ;
Marmor, Schelomo ;
Hovertsen, Shane ;
Gronski, Jessica ;
McNeil, Chace ;
Feng, Ruoying ;
Guzman, Gabriel ;
Abdelwahab, Nermine ;
King, Samantha ;
Tamariz, Leonardo ;
Meehan, Thomas ;
Pendleton, Kathryn M. ;
Benson, Bradley ;
Vojta, Deneen ;
Tignanelli, Christopher J. .
LANCET HEALTHY LONGEVITY, 2021, 2 (01) :E34-E41
[4]   Anti-IL6R role in treatment of COVID-19-related ARDS [J].
Buonaguro, Franco Maria ;
Puzanov, Igor ;
Ascierto, Paolo Antonio .
JOURNAL OF TRANSLATIONAL MEDICINE, 2020, 18 (01)
[5]   Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome [J].
Cameron, Mark J. ;
Ran, Longsi ;
Xu, Luoling ;
Danesh, Ali ;
Bermejo-Martin, Jesus F. ;
Cameron, Cheryl M. ;
Muller, Matthew P. ;
Gold, Wayne L. ;
Richardson, Susan E. ;
Poutanen, Susan M. ;
Willey, Barbara M. ;
DeVries, Mark E. ;
Fang, Yuan ;
Seneviratne, Charit ;
Bosinger, Steven E. ;
Persad, Desmond ;
Wilkinson, Peter ;
Greller, Larry D. ;
Somogyi, Roland ;
Humar, Atul ;
Keshavjee, Shaf ;
Louie, Marie ;
Loeb, Mark B. ;
Brunton, James ;
McGeer, Allison J. ;
Kelvin, David J. .
JOURNAL OF VIROLOGY, 2007, 81 (16) :8692-8706
[6]   Overview of lethal human coronaviruses [J].
Chen, Bin ;
Tian, Er-Kang ;
He, Bin ;
Tian, Lejin ;
Han, Ruiying ;
Wang, Shuangwen ;
Xiang, Qianrong ;
Zhang, Shu ;
El Arnaout, Toufic ;
Cheng, Wei .
SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2020, 5 (01)
[7]   The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease [J].
Chen, Li ;
Hao, Guang .
CARDIOVASCULAR RESEARCH, 2020, 116 (12) :1932-1936
[8]   Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome [J].
Chien, Jung-Yien ;
Hsueh, Po-Ren ;
Cheng, Wern-Cherng ;
Yu, Chong-Jen ;
Yang, Pan-Chyr .
RESPIROLOGY, 2006, 11 (06) :715-722
[9]   Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress [J].
Clarke, Nicola E. ;
Belyaev, Nikolai D. ;
Lambert, Daniel W. ;
Turner, Anthony J. .
CLINICAL SCIENCE, 2014, 126 (7-8) :507-516
[10]   Hosts and Sources of Endemic Human Coronaviruses [J].
Corman, Victor M. ;
Muth, Doreen ;
Niemeyer, Daniela ;
Drosten, Christian .
ADVANCES IN VIRUS RESEARCH, VOL 100, 2018, 100 :163-188