Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1-Immunometabolism-CSCIED科技核心评价数据库-手机版

Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1

Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1

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DOI	10.1097/IN9.0000000000000078
刊名	Immunometabolism IJ
年，卷(期)	2026, 8(1)
作者	Maurmann, Rafael Moura; Davis, Kierstin; Mosalmanzadeh, Negin; Landvoigt Schmitt, Brenda; Pence, D.,
作者单位	Univ Memphis, Coll Hlth Sci, Memphis, TN 38152 USA
摘要	Background:Severe coronavirus disease 2019 (COVID-19) is characterized by a hyperinflammatory state associated with an exacerbated inflammatory activation of monocytes and macrophages in the respiratory tract. Metformin has been identified as a potent monocyte inflammatory suppressor, and it has been demonstrated to attenuate inflammation in COVID-19. The mechanisms underlying metformin's anti-inflammatory effects are, however, unclear. We thus sought to investigate metformin's main interactions and their respective isolated effects in modulating monocyte inflammatory response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulation.Methods:Classical human monocytes were isolated from healthy 18 to 40-year-old individuals and stimulated in vitro with recombinant spike protein subunit 1 (rS1) to assess glycolytic and oxidative metabolic responses by Seahorse extracellular flux analysis and inflammatory gene expression by quantitative polymerase chain reaction. Stimulated monocytes were either pretreated with metformin, rotenone, S1QEL, or A769662.Results:Monocytes stimulated in vitro with rS1 showed an increased glycolytic response associated with production of pro-inflammatory cytokines. Metformin pretreatment reduced glycolytic activation while partially suppressing inflammation. Rotenone-dependent mitochondrial complex I inhibition was not able to replicate the same effect, and neither was complex I-specific reactive oxygen species scavenging. Conversely, A769662-induced AMP-activated protein kinase (AMPK) activation led to suppressed glycolytic inflammatory response and cytokine expression pattern similar to metformin, thus suggesting AMPK modulation as a possible central component for metformin's mode of action upon S1 stimulation.Conclusions:In summary, further investigation into the interactions underlying AMPK activity on monocytes in the context of SARS-CoV-2 may provide a better elucidation of metformin's anti-inflammatory effect.
Abstract	Background:Severe coronavirus disease 2019 (COVID-19) is characterized by a hyperinflammatory state associated with an exacerbated inflammatory activation of monocytes and macrophages in the respiratory tract. Metformin has been identified as a potent monocyte inflammatory suppressor, and it has been demonstrated to attenuate inflammation in COVID-19. The mechanisms underlying metformin's anti-inflammatory effects are, however, unclear. We thus sought to investigate metformin's main interactions and their respective isolated effects in modulating monocyte inflammatory response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulation.Methods:Classical human monocytes were isolated from healthy 18 to 40-year-old individuals and stimulated in vitro with recombinant spike protein subunit 1 (rS1) to assess glycolytic and oxidative metabolic responses by Seahorse extracellular flux analysis and inflammatory gene expression by quantitative polymerase chain reaction. Stimulated monocytes were either pretreated with metformin, rotenone, S1QEL, or A769662.Results:Monocytes stimulated in vitro with rS1 showed an increased glycolytic response associated with production of pro-inflammatory cytokines. Metformin pretreatment reduced glycolytic activation while partially suppressing inflammation. Rotenone-dependent mitochondrial complex I inhibition was not able to replicate the same effect, and neither was complex I-specific reactive oxygen species scavenging. Conversely, A769662-induced AMP-activated protein kinase (AMPK) activation led to suppressed glycolytic inflammatory response and cytokine expression pattern similar to metformin, thus suggesting AMPK modulation as a possible central component for metformin's mode of action upon S1 stimulation.Conclusions:In summary, further investigation into the interactions underlying AMPK activity on monocytes in the context of SARS-CoV-2 may provide a better elucidation of metformin's anti-inflammatory effect.
关键词	immunometabolism; metformin; AMPK; severe acute respiratory syndrome coronavirus-2; innate immunity
KeyWord	immunometabolism; metformin; AMPK; severe acute respiratory syndrome coronavirus-2; innate immunity
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Maurmann, Rafael Moura; Davis, Kierstin; Mosalmanzadeh, Negin; Landvoigt Schmitt, Brenda; Pence, D.. Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1 [J]. Immunometabolism. 2026; 8; (1). - .

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