The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis.
We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of fasudil prevented the development of EAE induced by proteolipid protein (PLP) p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was significantly reduced, together with a downregulation of interleukin (IL)-17 and a marked decrease of the IFN-gamma/IL-4 ratio. Immunohistochemical examination also disclosed a marked decrease of inflammatory cell infiltration, and attenuated demyelination and acute axonal transaction. These results may provide a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new therapy for multiple sclerosis.
Sun
Xiaojia
X
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Minohara
Motozumi
M
Kikuchi
Hitoshi
H
Ishizu
Takaaki
T
Tanaka
Masahito
M
Piao
Hua
H
Osoegawa
Manabu
M
Ohyagi
Yasumasa
Y
Shimokawa
Hiroaki
H
Kira
Jun-Ichi
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000037:antagonists & inhibitors / Q000276:immunology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D054460:rho-Associated Kinases
D018836:Inflammation Mediators; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; D018991:Myelin Proteolipid Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C435023:myelin proteolipid protein (139-151); D015847:Interleukin-4; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil