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Published on: January 7, 2019
Remifentanil Protects against Lipopolysaccharide-Induced Inflammation through PARP-1/NF-κB Signaling Pathway
Jian-Ning Zhang1, Yang Ma1, Xi-Yan Wei1
1Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Abstract:
Sepsis is a leading cause of death in patients with severe infection worldwide. Remifentanil is an ultra-short-acting, potent opioid analgesic. In the study, we aimed to investigate the role and underlying mechanism of remifentanil in lipopolysaccharide- (LPS-) induced inflammation in human aortic endothelial cells (HAECs). HAECs were pretreated with phosphate-buffered saline (PBS) or remifentanil (2.5 μM) for 30 min, then stimulated by LPS (10 μg/ml) for another 24 h. Poly(ADP-ribose) polymerase 1 (PARP-1) was inhibited by small interfering RNA (siRNA). Superoxide anion production and DNA damage were analyzed by dihydroethidium (DHE) staining and comet assay. The inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), PARP-1, poly(ADP-ribose) (PAR), and nuclear factor-kappa B p65 (NF-κB p65) expressions were analyzed by RT-PCR or western blotting analysis. NF-κB p65 nuclear translocation was assessed by immunofluorescence. Compared with the control group, pretreatment with remifentanil significantly reduced superoxide anion production and DNA damage, with downregulation of iNOS, ICAM-1, and PARP-1 expressions as well as PAR expression. Moreover, pretreatment with PARP-1 siRNA or remifentanil inhibited LPS-induced NF-κB p65 expression and nuclear translocation. Remifentanil reduced LPS-induced inflammatory response through PARP-1/NF-κB signaling pathway. Remifentanil might be an optimal choice of analgesia in septic patients.
Insights
Remifentanil, an opioid analgesic, reduces inflammation in sepsis by inhibiting the poly(ADP-ribose) polymerase 1 (PARP-1) and nuclear factor-kappa B (NF-κB) signaling pathway. This suggests remifentanil may be suitable for pain management in septic patients.
Area of Science:
- Biomedical Science
- Pharmacology
- Cell Biology
Background:
- Sepsis is a life-threatening condition with high mortality worldwide.
- Effective analgesia is crucial for managing sepsis patients.
- Lipopolysaccharide (LPS) is a key inducer of inflammation in sepsis models.
Purpose of the Study:
- To investigate the anti-inflammatory effects of remifentanil in LPS-induced inflammation.
- To elucidate the underlying molecular mechanisms of remifentanil's action.
- To evaluate remifentanil's potential as an analgesic in sepsis.
Main Methods:
- Human aortic endothelial cells (HAECs) were treated with remifentanil and/or LPS.
- Poly(ADP-ribose) polymerase 1 (PARP-1) was inhibited using siRNA.
- Cellular responses including superoxide anion production, DNA damage, and inflammatory marker expression (iNOS, ICAM-1, PARP-1, PAR, NF-κB p65) were analyzed.
Main Results:
- Remifentanil pretreatment significantly reduced LPS-induced superoxide anion production and DNA damage.
- Remifentanil downregulated the expression of iNOS, ICAM-1, PARP-1, and PAR.
- Remifentanil, similar to PARP-1 inhibition, suppressed LPS-induced NF-κB p65 expression and nuclear translocation.
Conclusions:
- Remifentanil exerts anti-inflammatory effects by inhibiting the PARP-1/NF-κB signaling pathway.
- Remifentanil demonstrates potential as an effective analgesic option for sepsis patients.
- Further research is warranted to confirm remifentanil's efficacy and safety in clinical sepsis management.
