Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil
Authors: Mingfang Guo
Haifei Zhang
Ling Feng
Yueting Liu
Yong Xie
Cungen Ma
Shaowei Hou
Baoguo Xiao
Jiezhong Yu
Chunyun Liu
Jian Meng
Yanhua Li
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Fasudil; Rho kinase inhibitor; experimental autoimmune encephalomyelitis; multiple sclerosis; CD4(+)IL-17(+) T cells
Affiliations: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.

Abstract:  We observed the therapeutic effect of Fasudil and explored its mechanisms in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Fasudil, a selective Rho kinase (ROCK) inhibitor, was injected intraperitoneally at 40 mg/kg/d in early and late stages of EAE induction. Fasudil ameliorated the clinical severity of EAE at different stages, and decreased the expression of ROCK-II in spleen, accompanied by an improvement in demyelination and inhibition of inflammatory cells. Fasudil mainly inhibited CD4(+)IL-17(+) T cells in early treatment, but also elevated CD4(+)IL-10(+) regulatory T cells and IL-10 production in late treatment. The treatment of Fasudil shifted inflammatory M1 to anti-inflammatory M2 macrophages in both early and late treatment, being shown by inhibiting CD16/32, iNOS, IL-12, TLR4 and CD40 and increasing CD206, Arg-1, IL-10 and CD14 in spleen. By using Western blot and immunohistochemistry, iNOS and Arg-1, as two most specific markers for M1 and M2, was inhibited or induced in splenic macrophages and spinal cords of EAE mice treated with Fasudil. In vitro experiments also indicate that Fasudil shifts M1 to M2 phenotype, which does not require the participation or auxiliary of other cells. The polarization of M2 macrophages was associated with the decrease of inflammatory cytokine IL-1β, TNF-α and MCP-1. These results demonstrate that Fasudil has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses. 

Retracted: No

PubPeer comments:
 Could the authors confirm that the materials described in [14]-[16] are MOFs?  Among these strategies, SBU method is one of the most effective methods to synthesized new MOFs with predictable structures [14-16]. - [14] Y. Feng, H. Fan, Z. Zhong, H. Wang, D. Qiu, Inorg. Chem. 55 (2016) 11987. ** Cd3(MoO4)(TeO3)2: A Polar 3D Compound Containing d10u2013d0 SCALP-Effect Cations ** - [15] Y. Feng, M. Li, H. Fan, Q. Huang, D. Qiu, H. Shi, Dalton Trans. 44 (2015) 894. ** A novel open-framework copper borophosphate containing 1-D borophosphate anion with 10-MR windows and 12-MR channels ** - [16] C.W. Duan, L.X. Hu, J.L. Ma, J. Mater. Chem. 6 (2018) 6309. ** Ionic liquids as an efficient medium for the mechanochemical synthesis of u03b1-AlH3 nano-composites ** , 
 This is one of a large number of coordination-chemistry papers that appear to have all been written according to a template. - Most draw on two papers by Y. Feng et al. and one by C.-W. Duan et al to illustrate the broad range of applications and properties of MOFs. Notably, these are not papers about MOFs. - - Y. Feng, H. Fan, Z. Zhong, H. Wang, D. Qiu, Inorg. Chem. 2016, 55, 11987u201311992.  Cd3(MoO4)(TeO3)2: A Polar 3D Compound Containing d10-d0 SCALP-Effect Cations - - Y. Feng, M. Li, H. Fan, Q. Huang, D. Qiu, H. Shi, Dalton Trans. 2015, 44, 894u2013897.  A Novel Open-Framework Copper Borophosphate Containing 1-D Borophosphate Anion with 10-MR Windows and 12-MR Channels - - C. W. Duan, L. X. Hu, J. L. Ma, J. Mater. Chem. A 2018, 6, 6309u20136318  Ionic liquids as an efficient medium for the mechanochemical synthesis of u03b1-AlH3 nano-composites - The cluster is sometimes accompanied by less relevant references and clusters of references. Frequently co-occuring papers include - - Duan CW, Cao YZ, Hu LX, Fu D, Ma JL (2019)  Synergistic effect of TiF3 on the dehydriding property of a-AlH3 nano-composite . - - K. Wang, J. Pang, L. Li, S. Zhou, Y. Li, T. Zhang, Front. Chem. Sci. Eng. 2018, 12, 376u2013382.  Synthesis of hydrophobic carbon nanotubes reduced graphene oxide composite films by flash light irradiation - - K. Wu, K. Du, G. Hu, J. Mater. Chem. A 2018, 6, 1057u20131066  Red-blood-cell-like (NH4) [Fe2(OH)(PO4)2]u00b72H2O particles: Fabrication and application in high-performance LiFePO4 cathode materials - - Yin K, Chu DK, Dong XR, Wang C, Duan JA, He J (2017)  Femtosecond laser induced robust periodic nanoripples structured mesh for highly efficient oil-water separation . Nanoscale 9:14229u201314235. - - Davila-Manzanilla SG, Figueroa-de-Paz Y, Mejia C, Ruiz-Azuara L (2017)  Synergistic effects between a copper-based metal Casiopeu00edna III-Ia and cisplatin . Eur J Med Chem 129:266u2013274 - The vast majority of email identities for corresponding authors were formed by taking an underscore-separated name and appending **666** or 66 . I am advised that these are auspicious numbers with positive associations. So one possibility is that the authors all decided independently to generate email accounts with this format. The alternative is that *some outside contractor* handled the task of negotiating with journals (generating these disposable accounts in the process) - perhaps also the task of writing the manuscripts, using a single Bibliography file to save time. The complete list [is here] . ,