tetano
Editor, Senior Moderator
Inflamm Res
. 2021 Jun 4.
doi: 10.1007/s00011-021-01473-y. Online ahead of print.
The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications
Nohora Cristina Ayola-Serrano[SUP] #[/SUP][SUP] 1 [/SUP], Namrata Roy[SUP] #[/SUP][SUP] 2 [/SUP], Zareena Fathah[SUP] #[/SUP][SUP] 3 [/SUP], Mohammed Moustapha Anwar[SUP] #[/SUP][SUP] 4 [/SUP], Bivek Singh[SUP] 5 [/SUP], Nour Ammar[SUP] 6 [/SUP], Ranjit Sah[SUP] 7 [/SUP], Areej Elba[SUP] 6 [/SUP], Rawan Sobhi Utt[SUP] 8 [/SUP], Samuel Pecho-Silva[SUP] 9 10 11 [/SUP], Alfonso J Rodriguez-Morales[SUP] 12 13 14 15 [/SUP], Kuldeep Dhama[SUP] 16 [/SUP], Sadeq Quraishi[SUP] 17 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1β [IL-1β]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.
Keywords: 5-LOX inhibitors; 5-lipoxygenase; COVID-19; CRS; SARS-CoV-2.
. 2021 Jun 4.
doi: 10.1007/s00011-021-01473-y. Online ahead of print.
The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications
Nohora Cristina Ayola-Serrano[SUP] #[/SUP][SUP] 1 [/SUP], Namrata Roy[SUP] #[/SUP][SUP] 2 [/SUP], Zareena Fathah[SUP] #[/SUP][SUP] 3 [/SUP], Mohammed Moustapha Anwar[SUP] #[/SUP][SUP] 4 [/SUP], Bivek Singh[SUP] 5 [/SUP], Nour Ammar[SUP] 6 [/SUP], Ranjit Sah[SUP] 7 [/SUP], Areej Elba[SUP] 6 [/SUP], Rawan Sobhi Utt[SUP] 8 [/SUP], Samuel Pecho-Silva[SUP] 9 10 11 [/SUP], Alfonso J Rodriguez-Morales[SUP] 12 13 14 15 [/SUP], Kuldeep Dhama[SUP] 16 [/SUP], Sadeq Quraishi[SUP] 17 [/SUP]
Affiliations
- PMID: 34086061
- DOI: 10.1007/s00011-021-01473-y
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1β [IL-1β]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.
Keywords: 5-LOX inhibitors; 5-lipoxygenase; COVID-19; CRS; SARS-CoV-2.