Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications

Banu, Nehla; Panikar, Sandeep Surendra; Leal, Lizbeth Riera; Leal, Annie Riera

doi:10.1016/j.lfs.2020.117905

Cited by 155 publications

(153 citation statements)

References 185 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…ACE2 reduces the angiotensin II levels, which have directly pro-inflammatory and pro-oxidant properties. ACE2 thus plays a pivotal role in the modulation of excessive inflammatory responses [97,98]. ACE2 exerts beneficial effects in a number of pathological situations, including SARS-CoV-2 infection, as it directly protects the lungs against ARDS [99].…”

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

“…Virus-mediated ACE2 downregulation can diminish its activity, attenuate its anti-inflammatory properties, and reinforce the angiotensin II impacts in the susceptible patients [97]. Under inflammatory conditions, the transmembrane disintegrin ADAM17 can also cleave the membrane-linked ACE2, which releases ACE2 into circulation or interstitium [98,100].…”

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

“…SARS-CoV infection, as well as inflammatory cytokines such as IL-1β and TNF-α, can enhance ACE2 shedding [101]. The soluble ACE2 may be directly contributed to the inflammatory reactions of SARS-CoV, and perhaps SARS-CoV-2 [98]. The reduced activity of pulmonary ACE2 was related to the ALI/ARDS [98,99].…”

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

See 2 more Smart Citations

Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

et al. 2020

View full text Add to dashboard Cite

The COVID-19-, SARS-and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARSand MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development of COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment. 1. Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)mediated COVID-19 has emerged during the late 2019 and caused a serious public health threat, forcing the WHO to announce the SARS-CoV-2 outbreak as a pandemic [1]. SARS-CoV-2, as a member of the coronavirus family, is an enveloped virus containing a positive-sense single-stranded RNA molecule

show abstract

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

Section: Angiotensin Induces Inflammatory Responses In Monocytes and mentioning

confidence: 99%

See 1 more Smart Citation

Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…1). Based on our model, SARS-CoV-2 infection of AEC leads to downregulation of ACE2 and increased geneexpression of IL-6 and TNF-α in AEC via SARS-CoV2-ACE2-TACE and SARS-CoV2-PRR-NF κ B interactions [3]. IL6-sIL-6Rα, IL-1β, and sTNF-α are then released on the luminal and abluminal sides of epithelial cells.…”

Section: Dear Editormentioning

confidence: 93%

Covid-19 Pathogenies: “Epithelial-endothelial-pericyte” cross-talk hypothesis

Jain¹

2020

Preprint

View full text Add to dashboard Cite

“…Normally, the M1/M2 polarization of macrophages maintains a dynamic equilibrium. When virulent bacteria or viral infections or overmuch inflammatory molecules irritation, this balance is disrupted, excessive M1 polarization of macrophages will generate redundant inflammatory factors, causing systemic inflammatory response syndrome (SIRS, namely sepsis) and MOF (8). Therefore, it is particularly vital to skew the macrophage polarization and avoid excessive M1-polarization, thus reduce the inflammatory response and promote tissue remodeling.…”

mentioning

confidence: 99%

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Wang¹,

Cao

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTMacrophage are indispensable regulator cells in inflammatory response. Macrophage polarization and its secreted inflammatory factors have affinity with the outcomes of inflammation. Luteolin, a flavonoid abundant in plants has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarization of BMDM to suppress inflammation is still veiled. The purpose of this study was to observe the effects of luterolin on the polarity of BMDM derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism of luteolin regulating the BMDM polarity. M1-polarized BMDM were induced by LPS+IFN-γ, M2-polarization were stimulated with IL-4. BMDM morphology was observed by laser confocal microscopy; levels of BMDM differentiation and CD11c or CD206 on membrane surface were assessed by FCM; mRNA and protein of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. The isolated mouse bone marrow cells were successfully differentiated into BMDM, LPS+IFN-γ induced BMDM M1-phenotype polarization, and IL-4 induced its M2-phenotype polarization. After M1-polarized BMDM treated with luteolin, M1-type pro-inflammatory factors including IL-6, TNF-α□iNOS, CD86 were down-regulated while M2-type anti-inflammatory factors including IL-10, Arg1, CD206 were up-regulated; the expression of M1-type surface marker CD11c decreased, nevertheless, M2-type marker CD206 increased; levels of inflammatory signaling protein p-STAT1 and p-STAT6 were attenuated and enhanced respectively. Our study suggests luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin hold promise as an anti-inflammatory and immunomodulatory agent.

show abstract

Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications

Cited by 155 publications

References 185 publications

Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

Covid-19 Pathogenies: “Epithelial-endothelial-pericyte” cross-talk hypothesis

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Contact Info

Product

Resources

About