Mast cells (MCs) are hematopoietic cells developed from bone marrow progenitors in response to the ligand stem cell factor, a trans-membrane tyrosine kinase kit receptor. MCs are located virtually in all vascularized tissues and in proximity to neurons and play a decisive role in both innate and adaptive immune responses. Their activation is involved in oxidative stress correlated with infection and inflammation. Pro-inflammatory cytokines are secreted by MCs after physiologic and psychological stress due to virus infection, including SARS-CoV-2. MCs, along with macrophages and pulmonary alveolar epithelial cells, are the main targets attacked by the coronavirus. COVID-19 induced by SARS-CoV-2 causes inflammatory stress which activates MCs to secrete corticotrophin-releasing hormone (CRH), SP, IL-6, TNF, and IL-1. Toll-like receptor (TLR) virus activation in MCs leads to pro-inflammatory cytokine generation without degranulation, an effect that can be inhibited by IL-10, IL-4, IL-1Ra and IL-37. TLR has the ability to recognize extracellular PAMPs by causing the transcription of NLRP, pro-IL-1, and other pro-inflammatory cytokines. The multi-protein complex, comprising pro-caspase-1, activates caspase-1 which in turn activates pro-IL-1 that is transformed into highly inflammatory mature IL-1. In COVID-19, viral RNA is specifically recognized by TLR, followed by recruiting the signal transfer proteins MyD88, IRAK, IKK and TRAF6 which can activate the NF-κB, resulting in transcription of the pro-inflammatory cytokines IL-1 and TNF, responsible for the “cytokine storm” phenomenon. Meanwhile, a new variant of the coronavirus-19 called C.1.2. has been discovered in the United States in the past few days, the effects of which are unknown, and it is therefore of great concern. Researchers are now testing it on immune cells to see if they react and are comparing it to a delta variant. Thus, from the existing data in biomedical literature, we can conclude that the suppression of pro-inflammatory cytokines in viral infections (including COVID-19) mediated by MCs represents a promising therapy not only in this field of medicine, but also in autoimmune, allergic, and cardiovascular disorders, as well as tumor inflammation where MCs play a key role.

Mast cell virus infection and inflammatory cytokines

Conti P.;Calvisi V.;Trimarchi M.
2021

Abstract

Mast cells (MCs) are hematopoietic cells developed from bone marrow progenitors in response to the ligand stem cell factor, a trans-membrane tyrosine kinase kit receptor. MCs are located virtually in all vascularized tissues and in proximity to neurons and play a decisive role in both innate and adaptive immune responses. Their activation is involved in oxidative stress correlated with infection and inflammation. Pro-inflammatory cytokines are secreted by MCs after physiologic and psychological stress due to virus infection, including SARS-CoV-2. MCs, along with macrophages and pulmonary alveolar epithelial cells, are the main targets attacked by the coronavirus. COVID-19 induced by SARS-CoV-2 causes inflammatory stress which activates MCs to secrete corticotrophin-releasing hormone (CRH), SP, IL-6, TNF, and IL-1. Toll-like receptor (TLR) virus activation in MCs leads to pro-inflammatory cytokine generation without degranulation, an effect that can be inhibited by IL-10, IL-4, IL-1Ra and IL-37. TLR has the ability to recognize extracellular PAMPs by causing the transcription of NLRP, pro-IL-1, and other pro-inflammatory cytokines. The multi-protein complex, comprising pro-caspase-1, activates caspase-1 which in turn activates pro-IL-1 that is transformed into highly inflammatory mature IL-1. In COVID-19, viral RNA is specifically recognized by TLR, followed by recruiting the signal transfer proteins MyD88, IRAK, IKK and TRAF6 which can activate the NF-κB, resulting in transcription of the pro-inflammatory cytokines IL-1 and TNF, responsible for the “cytokine storm” phenomenon. Meanwhile, a new variant of the coronavirus-19 called C.1.2. has been discovered in the United States in the past few days, the effects of which are unknown, and it is therefore of great concern. Researchers are now testing it on immune cells to see if they react and are comparing it to a delta variant. Thus, from the existing data in biomedical literature, we can conclude that the suppression of pro-inflammatory cytokines in viral infections (including COVID-19) mediated by MCs represents a promising therapy not only in this field of medicine, but also in autoimmune, allergic, and cardiovascular disorders, as well as tumor inflammation where MCs play a key role.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/187612
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