title: ROCK inhibitor abolishes the antibody response in experimental autoimmune myasthenia gravis.
abstract: The Rho/Rho kinase (ROCK) pathway serves as molecular switches in many biological processes including the immune response. ROCK inhibitors lead to amelioration of some autoimmune diseases. The present study was designed to define whether a selective ROCK inhibitor, fasudil, was effective in experimental autoimmune myasthenia gravis (EAMG) and investigate the underlying mechanisms. Here we found fasudil effectively attenuated the development of ongoing EAMG. Fasudil abolished the antibody production and function by decreasing follicular helper T cells and CD19(+) B cells, especially germinal center B cells. Moreover, fasudil reduced the expression of CD80 on lymph node mononuclear cells. These findings suggest the inhibition of ROCK might be a potential therapeutic strategy for antibody-mediated autoimmune diseases.
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Long-Tao
authors.initials: LT
authors.lastname: Yue
authors.affiliation: Department of Neurology, Jinan General Military Hospital, Second Military Medical University, Jinan 250031, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Miao
authors.affiliation: College of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Dou
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China. Electronic address: ruisheng_duan@yahoo.com.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Duan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000187:drug effects; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil
keywords: Antibody; Experimental autoimmune myasthenia gravis; Follicular helper T cells; Germinal center; Rho kinase inhibitor