Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB and ERK signaling pathways in BV2 cells
Authors: Yalong Dang
Yu Zhu
Yongsheng Xu
Jing Yang
Chun Zhang
Wentao Wu
Weiyi Li
Yanran Sun
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Tetrandrine; microglia; inflammation; lipopolysaccharide; IL1β
Affiliations: Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China., Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China., Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China., Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China., Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.

Abstract:  Background and objective: Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms. Study design/materials and methods: Cell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1β and TNFα. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins. Results: TET at optimal concentrations (0.1 µM, 0.5 µM or 1 µM) did not affect the cell viability. After TET pretreatment, the levels of IL1β and TNFα (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET. Conclusions: Our results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1β and TNFα by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma. 

Retracted: Yes

PubPeer comments:
null, 
 Peer 1 reporting back under full name. This article has been retracted today, five years after I reported this to the journal in August 2014. See: https: journals.plos.org plosone article?id=10.1371 journal.pone.0224894 The retraction notice reads:  After this article [1] was published, the following issues were raised about the western blot results reported in Figures 6 and 7 (...). The authors provided image files in support of the p65, p-p65, IKK, p-IKK, u03b2 -actin panels in Figure 6A, and for the p-JNK and u03b2-actin panels of Figure 7A. The first author confirmed that in preparing figures they rearranged lanes and edited the images to remove some background noise. For Figure 6A, the raw images supported the overall results reported in the figure, and clarified that lanes were rearranged when preparing the IKK, p-IKK, and u03b2-actin panels. The first author noted that lane 4 data were duplicated in error in lane 5 in the p-IKK panel. Per our editorial assessment, results in lanes 1u20134 of the Figure 7A p-JNK panel do not match the raw image data provided for this experiment. Lane 1 of this panel appears to duplicate the data in Figure 6A, p-IKK, lane 1 and the raw image provided for the p-IKK experiment. The first author and corresponding author YZ confirmed this duplication and stated that this was due to an error in figure preparation. The first author also commented that they erased part of the image above the band shown in lane 3 of the Figure 7A p-JNK panel. Questions remain as to the data reported in lanes 2 and 4 of the p-JNK figure panel. In light of the remaining concerns about the validity and reliability of the results reported in Figure 7A and the confirmed manipulation of background image data in the western blot panels of Figure 6 and 7, the PLOS ONE Editors retract this article. The authors apologize for the figure concerns and commented that they had poor knowledge of PLOS ONEu2019s guidelines and of figure preparation best practice when they prepared the manuscript. YD and YZ notified the journal that all authors agreed with the retraction, but are confident in the findings and stand by the published results. CZ confirmed their agreement, the other authors did not reply to the journal directly or could not be reached. ,