Biomaterial Database

Suppression of neuro inflammation in experimental autoimmune encephalomyelitis by glia maturation factor antibody. 2011

Smita Zaheer, and Yanghong Wu, and Shailendra K Sahu, and Asgar Zaheer

Division of Neurochemistry and Neurobiology, Department of Neurology, University of Iowa, Iowa City, IA 52242, USA.

Glia maturation factor (GMF), a protein primarily localized in the central nervous system (CNS) was isolated, sequenced and cloned in our laboratory. We previously demonstrated that GMF mediates the experimental autoimmune encephalomyelitis (EAE)-induced production of pro-inflammatory cytokines and chemokines in the central nervous system of mice. In the present study we show that immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) caused an early onset (days 7-9 post immunization) and severe EAE with a mean peak score of 3.5 ± 0.5 in mice. Neutralization of GMF with four injections of anti-GMF antibody 5 to 11 days post immunization delayed the time of onset (days 12-14 post immunization) and significantly reduced the severity of EAE (mean peak score of 1.5 ± 0.4). Consistent with these clinical scores, histological examination of the CNS of these mice revealed profound differences between GMF-antibody treated mice and isotype matched control-antibody treated mice. Histological analysis of the spinal cord and brain showed severe inflammation and demyelination in the control antibody-treated mice whereas significantly reduced inflammation and demyelination was detected in GMF-antibody-treated mice at days 8, 16, and 24 post immunization. The decreased incidence and reduced severity of EAE in GMF-antibody-treated mice was consistent with the significantly reduced expressions of pro-inflammatory cytokines and chemokines. Our overall results demonstrate that neutralization of endogenous GMF with an affinity purified GMF antibody significantly decreased the inflammation, severity and progression of immunization induced active, passive and relapsing-remitting EAE. Treatment of mice with isotype-matched control antibody did not have any effect on EAE. Taken together, these results demonstrate the critical role of GMF in EAE, and GMF antibody as a potent anti-inflammatory therapeutic agent for effectively suppressing EAE in mouse models of major types of multiple sclerosis (MS).

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D004681	Encephalomyelitis, Autoimmune, Experimental	An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)	Autoimmune Encephalomyelitis, Experimental,Encephalomyelitis, Allergic,Encephalomyelitis, Experimental Autoimmune,Allergic Encephalomyelitis,Allergic Encephalomyelitis, Experimental,Autoimmune Experimental Encephalomyelitis,Experimental Allergic Encephalomyelitis,Experimental Autoimmune Encephalomyelitis,Encephalomyelitis, Autoimmune Experimental,Encephalomyelitis, Experimental Allergic,Experimental Allergic Encephalomyelitides,Experimental Encephalomyelitis, Autoimmune
D004797	Enzyme-Linked Immunosorbent Assay	An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.	ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006023	Glycoproteins	Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins.	C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000906	Antibodies	Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).