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Multiple Sclerosis, Vol. 12, No. 2, 149-168 (2006)
DOI: 10.1191/135248506ms1251oa
© 2006 SAGE Publications

Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures

R P Lisak

Department of Neurology, Wayne State University, Detroit, MI, USA, Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA, rlisak{at}med.wayne.edu

J A Benjamins

Department of Neurology, Wayne State University, Detroit, MI, USA, Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA, Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI, USA

B Bealmear

Department of Neurology, Wayne State University, Detroit, MI, USA

B Yao

The Applied Genomics and Technology Center, Wayne State University, Detroit, MI, USA

S Land

The Applied Genomics and Technology Center, Wayne State University, Detroit, MI, USA, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA

L Nedelkoska

Department of Neurology, Wayne State University, Detroit, MI, USA

D Skundric

Department of Neurology, Wayne State University, Detroit, MI, USA, Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA

Cytokines secreted within the central nervous system (CNS) are important in the development of multiple sclerosis (MS) lesions. The balance between Th1, monocyte/macrophage (M/M) and Th2 cytokines in the CNS may be pivotal in determining the outcome of lesion development. We examined the effects of mixtures of cytokines on gene expression by CNS glial cells, as mixtures of cytokines are present in MS lesions, which in turn contain mixtures of glial cells. In this initial analysis by gene array, we examined changes at 6 hours to identify early changes in gene expression that represent primary responses to the cytokines. Rat glial cells were incubated with mixtures of Th1, M/M and Th2 cytokines for 6 hours and examined for changes in early gene expression employing microarray gene chip technology. A minimum of 814 genes were differentially regulated by one or more of the cytokine mixtures in comparison to controls, including changes in expression in a large number of genes for immune system-related proteins. Expression of the proteins for these genes likely influences development and inhibition of MS lesions as well as protective and regenerative processes. Analysing gene expression for the effects of various combinations of exogenous cytokines on glial cells in the absence of the confounding effects of inflammatory cells themselves should increase our understanding of cytokine-induced pathways in the CNS.

Key Words: adhesion molecules • chemokines • cytokines • glial cells • inflammation • major histocompatibility complex • microarrays • prostaglandins


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R. P. Lisak
Neurodegeneration in multiple sclerosis: Defining the problem
Neurology, May 29, 2007; 68(22_suppl_3): S5 - S12.
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