In vitro screening of NADPH oxidase inhibitors and in vivo effects of L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice

Title
In vitro screening of NADPH oxidase inhibitors and in vivo effects of L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice
Authors
L. Kandagaddala서지은마무눌 하크임혜연강민정정병화T. A. patterson권오승
Keywords
EAE; Multiple sclerosis; L-Leucinethiol; MMP-9; NADPH Oxidase; Cytokine
Issue Date
2012-03
Publisher
Society of Toxicology
Abstract
Experimental autoimmune encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system, shares many pathological and clinical similarities with multiple sclerosis (MS), and thus represents an attractive animal model for this disease. The objectives of this study were i) to evaluate the suppressive effects of L‐leucinethiol (LeuSH), a metalloprotease inhibitor on EAE‐induced mice and ii) to study the effects of LeuSH on matrix metalloproteinase‐9 (MMP‐9), NADPH oxidase and cytokines (IFN‐γ, IL‐5 and IL‐10) in tissues and plasma of EAE mice as a measure of potential markers associated with EAE disease. C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG35‐55) peptide in complete Freund’s adjuvant to induce EAE. MOG33‐55 was administered subcutaneously on two sites over the back. Pertussis toxin was administered intraperitoneally immediately after MOG35‐55 injection and again two days later. A significant difference was observed in body weights and clinical signs of LeuSH (8 mg/kg) administered EAE‐induced mice compared to EAE‐induced mice. MMP‐9, NADPH oxidase and cytokines were measured in central nervous system tissues, peripheral tissues and plasma of EAE‐induced mice. The findings of this study include alterations in the enzymatic expression of MMP‐9, NADPH oxidase and cytokine levels in the brain, spinal cord, spleen, thymus and plasma of inhibitor‐treated EAE mice as well as EAE‐induced mice. The enzyme activities of NADPH oxidase were inhibited by LeuSH. From these results, it can be considered that LeuSH acts as one of the antigen candidates in ameliorating the clinical symptoms of EAE disease in mice.
URI
http://pubs.kist.re.kr/handle/201004/42149
Appears in Collections:
KIST Publication > Conference Paper
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