Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells
Authors: Yeon Ha Kim
Jae-Chaul You
Ji-Uk Yoon
Ah-Reum Cho
Eun-Jung Kim
Ji-Hye Ahn
Sang-Hun Shin
Journal: International Journal of Medical Sciences (2020)
Discipline: CLINICAL MEDICINE
Keywords: Amnion; Dexmedetomidine; Inflammation; NF-Œ∫B; p38.
Affiliations: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan, Korea., Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute, Yangsan, Korea., Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea., Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea., Department of Anesthesia and Pain Medicine, Pusan National University, School of Medicine, Yangsan, Republic of Korea.

Abstract:  Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-Œ∫B) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 ¬µg/ml) for 1 h and after then treated with LPS (1 ¬µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-Œ± and interlukin (IL)-1Œ≤. Protein expressions of COX-2, PGE2, p38 and NF-Œ∫B were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-Œ± and IL-1Œ≤. The activation of p38 and NF-Œ∫B was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-Œ∫B activation. 

Retracted: No

PubPeer comments:
 This paper makes use of  *The WISH human amnion cell line* which was  *purchased from the American Type Culture Collection* . But as it is known since 1968 and confirmed in the 1980 s this is a HeLa contaminated cell line. How someone can still make use of WISH as a model of an amniotic cell line 53 years after it has been known to be contaminated is baffling. Furthermore the ATCC site where the authors have obtained this cell line makes this fact very clear by stating; *This line was originally thought to be derived from normal amnion, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via HeLa cell contamination.* The authors state  *we used human amnion-derived WISH cells as a model for studying the effect of dexmedetomidine on the expression of inflammatory substances involved in preterm labor* Therefore all the conclusions of this paper are invalid and this paper should be retracted. See the relevant [Cellosaurus entry] ,