Therapeutic potential of proteases in acute lung injury and respiratory distress syndrome via TLR4/Nrf2/NF-kB signaling modulation
Copyright © 2024 Elsevier B.V. All rights reserved..
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide. Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2, p38 MAPK, NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis, whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:267 |
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| Enthalten in: |
International journal of biological macromolecules - 267(2024), Pt 1 vom: 02. Apr., Seite 131153 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anwar, Hend Mohamed [VerfasserIn] |
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| Links: |
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| Themen: |
α chymotrypsin |
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| Anmerkungen: |
Date Revised 17.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ijbiomac.2024.131153 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370643496 |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide. Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2, p38 MAPK, NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis, whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute lung injury | |
| 650 | 4 | |a Acute respiratory distress syndrome | |
| 650 | 4 | |a Bacillus cereus protease | |
| 650 | 4 | |a Cytokine storm | |
| 650 | 4 | |a Lipopolysaccharides | |
| 650 | 4 | |a α chymotrypsin | |
| 700 | 1 | |a Salem, Gad Elsayed Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Abd El-Latief, Hanan M |e verfasserin |4 aut | |
| 700 | 1 | |a Osman, Amany Abd Elhameid |e verfasserin |4 aut | |
| 700 | 1 | |a Ghanem, Sahar K |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Haroon |e verfasserin |4 aut | |
| 700 | 1 | |a Chavanich, Suchana |e verfasserin |4 aut | |
| 700 | 1 | |a Darwish, Alshaymaa |e verfasserin |4 aut | |
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