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Apoptosis, also known as programmed cell death, is the major type of cell death involved in normal development, regeneration, proliferation and pathologic degeneration in the central nervous system (CNS). The apoptotic process can be divided further into two pathways depending on the involvement of mitochondria and related biochemical cascades. The internal(More)
Multiple sclerosis (MS) is thought to be an autoimmune disease. In healthy individuals, the T cells of the immune system, when activated by an infectious agent, regularly traffic across an intact blood-brain barrier, survey the CNS and then leave. In MS, for reasons that are only gradually being understood, certain events in the peripheral immune response(More)
CD40 is expressed on various immune cells, including macrophages and micro-glia. Aberrant expression of CD40 is associated with autoimmune inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. Interaction of Toll-like receptor-4 (TLR4) with the Gram-negative bacteria endotoxin lipopolysac-charide (LPS) results in the induction of an(More)
In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the(More)
Cellular adhesion molecules were initially defined as cell surface structures mediating cell-cell and cell-extracellular matrix (ECM) interactions. Adhesion molecules involved in immune responses have been classified into three families according to their structure: selectins, immunoglobulin (Ig) superfamily, and integrins. It has been well documented that(More)
The physiological function of interleukin-6 (IL-6) within the central nervous system (CNS) is complex; IL-6 exerts neurotrophic and neuroprotective effects, and yet can also function as a mediator of inflammation, demyelination, and astrogliosis, depending on the cellular context. In the normal brain, IL-6 levels remain low. However, elevated expression(More)
In this study, we demonstrate that transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10) and interleukin-6 (IL-6) inhibit tumor necrosis factor-alpha expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta alone had no effect on TNF-alpha expression, however, TGF-beta suppressed induction of TNF-alpha expression at both the(More)
The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce interleukin-6 (IL-6) gene expression in astrocytes. The molecular mechanism(s) by which these cytokines activate IL-6 expression was examined by transient transfection of the human IL-6 promoter linked to the reporter gene CAT (IL-6-CAT) in primary rat(More)
Chemokines constitute a superfamily of proteins that function as chemoattractants and activators of leukocytes. Astrocytes, the major glial cell type in the CNS, are a source of chemokines within the diseased brain. Specifically, we have shown that primary human astrocytes and human astroglioma cell lines produce the CXC chemokines IFN-gamma-inducible(More)
The antagonism between the cytokines IFN-gamma and IL-4 is well documented, but the mechanism by which IL-4 inhibits IFN-gamma-induced gene expression is not clearly understood. CD40 is a type I transmembrane protein that is critical for proper functioning of the immune system. We have previously shown that IFN-gamma is the most potent inducer of CD40(More)