Total glucosides of paeony suppresses experimental autoimmune uveitis in association with inhibition of Th1 and Th2 cell function in mice
Authors: Ding Lin
Bin Wang
Man-Qiang Peng
Wen-Hua Zhang
Xue-Tao Huang
Journal: International Journal of Immunopathology and Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Th1; Th2; experimental autoimmune uveitis; total glucosides of paeony; uveitis.
Affiliations: 1 Department of Ophthalmology, Changsha Aier Eye Hospital, Aier School of Ophthalmology, Central South University, Changsha, China., 2 Department of Ophthalmology, Huaihe Hospital of Henan University, Kaifeng, China., 3 Department of Dermatology, Huaihe Hospital of Henan University, Kaifeng, China., 4 Department of Ophthalmology, Third Xiangya Hospital of Central South University, Changsha, China.

Abstract:  Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-Œ≥), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-Œ≥, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases. 

Retracted: No

PubPeer comments:
 Figure 2 3 4 9: * Some panels appear to show an overlap. And that is an understatement. Boxes of the same color drawn by an image forensics program. Could the authors please check what might have gone wrong here?  This work was supported by the National Natural Science Foundation of China (No. 81572349, 81872080), Jiangsu Provincial Medical Talent (ZDRCA 2016055), the Science and Technology Department of Jiangsu Province (BK20181148, BK20161157) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).  , 
 Dear Elisabeth M Bik We really appreciate your careful reviewing of our article, which will be helpful for us to improve the quality of the study. The first author, Zun Mao, graduated and left our university, who mainly concentrated on the experiments of this research. I have contacted with her to proof the data and provide further explanation. , 
 Dear Prof. Elisabeth M Bik Thanks for your attention to this article and we deeply apologize that this careless mistake was not identified before publication. As the first author of this manuscript, I have proofed the original data to identify the source of these errors and analyzed it very carefully. We performed multiple parallel experiments in the migration and invasion assay 3 years ago. In order to ensure the same size of the image after scaling down, we put many images of later experiments on software related to early experiments for processing at the same time. We found that indeed some panels look similar with others. Due to the high similarity of the experiments themselves, part of them were could not be updated and saved in time after scaling down. Some original photos in early experiments might be covered by later photos. The error was generated when the Figure was assembled. We failed to identify this error during manuscript preparation. Thanks for catching this error and we deeply apologize that this careless mistake was not identified before publication. However, this mistake does not affect the conclusions of this report. We sincerely apologize for this mistake due to similarities between some panels. Attached are the corrected figures. For further clarity, we can repeat this part of our research and we will show you the updated result if necessary. At last, thanks for your attention and great comments for our work. Best wishes Zun Mao        , 
 #3 Thank you for responding. It will be interesting to see how the journal reacts to this new data. , 
 #3 Thank you for providing explanation and corrections. However, I do not accept your assertion that  this mistake does not affect the conclusions of this report . Just take a look of the two versions of your Fig 2H and Fig 3C. Please compare those panels questioned by Dr. Bik (#1) and the corresponding ones in you new version. We can see EVERY single one of these 17 images is so different now from then, some 53% of your images. If half of your images are likely highly unreliable, how can the study findings not be affected? In addition, repeating experiment or not is totally your call; however, a repeated set of experiments is a totally different set of data. For a new set of data, I d say please submit as a new manuscript, rather than piggybacking on the very wrong current published paper.  , 
 Thank you Dr Mao, for replacing the image panels in half of these images with new ones. However, I completely agree with Tulipa in Comment #5 that these replacements do not restore the faith in this data or in the remainder of the images. How can you say that these 17 mistakes do  not affect the conclusions of this report ? At best, it appears to show a lack of proper labeling of the photos obtained in your experiments. While one mistake could be attributed to an honest error, 17 of these mislabelings show a complete lack of keeping track of which photo belonged to which experiment. And that also casts great concerns about the labeling accuracy of the other data presented in your paper. Especially in the case of similar-looking photos, one should be extra careful in labeling them. That does not appear to have happened here. In fact, there is an additional duplication that I just noticed, and that is still present in the new set of figures. In Figure 2H, the SiHa siCSN6 migration and invasion panels still appear to overlap. I have marked that here in red:  At this point, I have lost all faith in the reliability of your paper, and I am deeply concerned about how casually you replaced these images with other data. ,