title: Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9, and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in Rats.
abstract: Dysfunctional expression of matrix metalloproteinase-9 (MMP-9) has been found to be closely associated with the experimental autoimmune neuritis (EAN). In this study, we explored the role of p38 mitogen-activated protein kinases (p38 MAPK) in the regulation of MMP-9 in sciatic nerves of EAN rats. We analyzed the expression changes of MMP-2, MMP-3, MMP-9, and mitogen-activated protein kinases (MAP kinases) in sciatic nerves of EAN rats and investigated the effect of p38 MAPK inhibitor (SB203580) on MMP-9 expression and pathological changes in EAN. Real-time PCR and western blot analyses showed that the expression of MMP-2 exhibited no significant changes throughout the course of EAN, while MMP-3 and MMP-9 presented the relatively increased expression compared with that in control group. MAP kinases, including p38 MAPK, ERK1/2, and JNK1/2, were activated in the sciatic nerve of EAN rats, and phosphorylated p38 MAPK showed similar patterns of expression to MMP-9. The expression of MMP-9 and phosphorylated p38 MAPK in sciatic nerves were in positive correlation with disease severity. In addition, SB203580 treatment significantly reduced the mRNA and protein level of MMP-9 in sciatic nerves on the peak phase of EAN. Inhibition of p38 MAPK also relieved neurologic severity and ameliorated pathological changes in EAN. In conclusion, SB203580 may ameliorate clinical deficit and pathological changes in EAN by reducing the MMP-9 expression in sciatic nerves, which suggest that p38 MAPK inhibitor such as SB203580 could be considered as a therapeutic candidate in autoimmune neuropathies.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 You Zheng Str, Nangang District, Harbin, 150001, Heilongjiang Province, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Hongping
authors.initials: H
authors.lastname: Chen
authors.forename: Shuainan
authors.initials: S
authors.lastname: Ma
authors.forename: Lixin
authors.initials: L
authors.lastname: Liang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Guo
authors.forename: Mingfei
authors.initials: M
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Guozhong
authors.initials: G
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000818:Animals; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009444:Neuritis, Autoimmune, Experimental / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000201:enzymology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C093642:SB 203580