J Dent Anesth Pain Med.  2019 Oct;19(5):253-260. 10.17245/jdapm.2019.19.5.253.

Anti-inflammatory effect of remifentanil in lipopolysaccharide–stimulated amniotic epithelial cells

Affiliations
  • 1Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute, Yangsan, Korea. anji1030@naver.com
  • 2Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.
  • 3Department of Integrated Biological Science, Pusan National University, Busan, Korea.

Abstract

BACKGROUND
Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells).
METHODS
WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B (NF-κB) and p38 and the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)2, and prostaglandin E (PGE)2 were quantified using western blotting and RT-PCR, respectively.
RESULTS
Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of NF-κB, and expression of COX2 and PGE2 in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of IL-1β and TNF-α expression was also observed with RT-PCR.
CONCLUSION
Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.

Keyword

Amnion; Inflammation; Preterm labor; Remifentanil

MeSH Terms

Abscess
Amnion
Anesthesia, General
Blotting, Western
Cell Survival
Dinoprostone
Epithelial Cells*
Facial Bones
Female
Humans
Inflammation
Interleukins
Neck
NF-kappa B
Obstetric Labor, Premature
Phosphorylation
Pregnancy
Pregnant Women
Premature Birth
Prostaglandin-Endoperoxide Synthases
Tumor Necrosis Factor-alpha
Uterine Contraction
Dinoprostone
Interleukins
NF-kappa B
Prostaglandin-Endoperoxide Synthases
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 Potential pathways from choriodecidual bacterial infection to myometrial contraction.

  • Fig. 2 In MTT assay, LPS and remifentanil did not affect the viability of WISH cells. WISH cells were incubated with remifentanil (0.001–1 µg/ml) and/or LPS (1 µg/ml) for 24 h. Data are presented as mean ± SD. All experimental results were repeated three times.

  • Fig. 3 Remifentanil inhibited phosphorylation of NF-κB and p38 (activated form of NF-κB and p38) in LPS-stimulated WISH cells using western blot analysis.##P < 0.01, ###P < 0.001 versus control group; *P < 0.05, **P < 0.01, ***P < 0.001 versus LPS group.

  • Fig. 4 RT-PCR analysis showed that co-treatment with remifentanil reduced the amount of mRNA expression of pro-inflammatory cytokines, such as IL-1β and TNF-α in the WISH cells at a very low concentration.#P < 0.05, ###P < 0.001 versus control group; *P < 0.05 versus LPS group.

  • Fig. 5 Remifentanil co-treatment decreased COX-2 and PGE2 production in LPS-stimulated WISH cells. It was measured using ELISA.#P < 0.05, ##P < 0.01 versus control group; *P < 0.05 versus LPS group.


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