Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR

Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used...

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Main Authors: Qin Liu, Guang-Hu Yang, Nai-Zhi Wang, Xin-Cheng Wang, Zhao-Long Zhang, Lu-Jun Qiao, Wen-Juan Cui
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024037216
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author Qin Liu
Guang-Hu Yang
Nai-Zhi Wang
Xin-Cheng Wang
Zhao-Long Zhang
Lu-Jun Qiao
Wen-Juan Cui
author_facet Qin Liu
Guang-Hu Yang
Nai-Zhi Wang
Xin-Cheng Wang
Zhao-Long Zhang
Lu-Jun Qiao
Wen-Juan Cui
author_sort Qin Liu
collection DOAJ
description Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms. Methods: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1β, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms. Results: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels. Conclusions: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.
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spelling doaj.art-dceef744f7cb4371a503a6952550718e2024-04-04T05:05:35ZengElsevierHeliyon2405-84402024-03-01106e27690Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIRQin Liu0Guang-Hu Yang1Nai-Zhi Wang2Xin-Cheng Wang3Zhao-Long Zhang4Lu-Jun Qiao5Wen-Juan Cui6Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, ChinaIntensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, ChinaDepartment of Respiratory and Critical Care Medicine, Jinan Central Hospital, Jinan, Shandong, 250013, ChinaIntensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, ChinaIntensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, ChinaIntensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, China; Corresponding author.Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, China; Corresponding author.Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms. Methods: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1β, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms. Results: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels. Conclusions: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.http://www.sciencedirect.com/science/article/pii/S2405844024037216m6ADexmedetomidineRAW264.7 cellsYTHDF1HOTAIR
spellingShingle Qin Liu
Guang-Hu Yang
Nai-Zhi Wang
Xin-Cheng Wang
Zhao-Long Zhang
Lu-Jun Qiao
Wen-Juan Cui
Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
Heliyon
m6A
Dexmedetomidine
RAW264.7 cells
YTHDF1
HOTAIR
title Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
title_full Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
title_fullStr Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
title_full_unstemmed Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
title_short Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR
title_sort dexmedetomidine suppressed the biological behavior of raw264 7 cells treated with lps by down regulating hotair
topic m6A
Dexmedetomidine
RAW264.7 cells
YTHDF1
HOTAIR
url http://www.sciencedirect.com/science/article/pii/S2405844024037216
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