Exposure of cigarette smoke condensate activates NLRP3 inflammasome in vitro and in vivo : A connotation of innate immunity and atherosclerosis
Copyright © 2020 Elsevier B.V. All rights reserved..
OBJECTIVE: Smoking is known to have detrimental effects on cardiovascular system. However, the potential molecular basis of smoking-induced atherosclerosis remains unclear. NLRP3 inflammasome is implicated in perpetuation of inflammatory response in atherosclerosis. Therefore, we aimed to explore the cytotoxic effects of cigarette smoke condensate (CSC) on the activation of NLRP3 inflammasome in vitro and in vivo.
METHODS: For in vitro study, the pro-atherogenic effects of CSC were evaluated in THP-1 monocytes with different dose concentrations (0.1, 1, 5, 10 and 20 µg/ml) for varied time periods (6, 12, 24 and 48 h). For in vivo study, 30 male C57BL/6J mice were employed. 6 mice were sacrificed for baseline investigations. 24 mice were randomly divided into four groups: Group-I:Control mice, Group-II:CSC model, Group-III:High-fat diet(HFD) model, and Group-IV:HFD + CSC model for 14 weeks (n = 6/group). The group-II and IV mice were injected with 720 µg CSC/20 g body weight intraperitoneally (6 days/week).
RESULTS: In vitro, higher dosage of CSC (20 µg/ml) was toxic to cells as significant decline in cell viability and proliferation was observed. Furthermore, the mRNA expression of NLRP3 inflammasome and its pro-cytokine levels were significantly augmented on CSC exposure in a dose-dependent manner but impeded in time-dependent manner. In vivo, CSC and HFD independently augmented the expression of NLRP3 inflammasome (~4-10 fold-change) along with pro-cytokine levels in Group-II and III vs Group-I mice whereas, HFD + CSC treatment demonstrated synergistic effects in Group-IV.
CONCLUSION: Our data suggest that CSC activates NLRP3 inflammasome in vitro and in vivo and collectively with HFD has synergistic effects in vivo that may promote atherosclerosis.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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Enthalten in: |
International immunopharmacology - 84(2020) vom: 22. Juli, Seite 106561 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Mehta, Sakshi [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 11.03.2021 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.intimp.2020.106561 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM309859212 |
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520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
520 | |a OBJECTIVE: Smoking is known to have detrimental effects on cardiovascular system. However, the potential molecular basis of smoking-induced atherosclerosis remains unclear. NLRP3 inflammasome is implicated in perpetuation of inflammatory response in atherosclerosis. Therefore, we aimed to explore the cytotoxic effects of cigarette smoke condensate (CSC) on the activation of NLRP3 inflammasome in vitro and in vivo | ||
520 | |a METHODS: For in vitro study, the pro-atherogenic effects of CSC were evaluated in THP-1 monocytes with different dose concentrations (0.1, 1, 5, 10 and 20 µg/ml) for varied time periods (6, 12, 24 and 48 h). For in vivo study, 30 male C57BL/6J mice were employed. 6 mice were sacrificed for baseline investigations. 24 mice were randomly divided into four groups: Group-I:Control mice, Group-II:CSC model, Group-III:High-fat diet(HFD) model, and Group-IV:HFD + CSC model for 14 weeks (n = 6/group). The group-II and IV mice were injected with 720 µg CSC/20 g body weight intraperitoneally (6 days/week) | ||
520 | |a RESULTS: In vitro, higher dosage of CSC (20 µg/ml) was toxic to cells as significant decline in cell viability and proliferation was observed. Furthermore, the mRNA expression of NLRP3 inflammasome and its pro-cytokine levels were significantly augmented on CSC exposure in a dose-dependent manner but impeded in time-dependent manner. In vivo, CSC and HFD independently augmented the expression of NLRP3 inflammasome (~4-10 fold-change) along with pro-cytokine levels in Group-II and III vs Group-I mice whereas, HFD + CSC treatment demonstrated synergistic effects in Group-IV | ||
520 | |a CONCLUSION: Our data suggest that CSC activates NLRP3 inflammasome in vitro and in vivo and collectively with HFD has synergistic effects in vivo that may promote atherosclerosis | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Atherosclerosis | |
650 | 4 | |a C57BL/6J mice | |
650 | 4 | |a Cell surface markers | |
650 | 4 | |a Cigarette smoke condensate | |
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700 | 1 | |a Bhatia, Alka |e verfasserin |4 aut | |
700 | 1 | |a Dhawan, Veena |e verfasserin |4 aut | |
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