IL‐1‐regulated responses in astrocytes: Relevance to injury and recovery

Abstract

In the central nervous system (CNS), the cellular processes of astrocytes make intimate contact with essentially all areas of the brain. They have also been shown to be functionally coupled to neurons, oligodendrocytes, and other astrocytes via both contact-dependent and non-contact-dependent pathways. These observations have led to the suggestion that a major function of astrocytes in the CNS is to maintain the homeostatic environment, thus promoting the proper functioning of the neuronal network. Inflammation in the CNS disrupts this process either transiently or permanently and, as such, is thought to be tightly regulated by both astrocytes and microglia. The remarkable role that single cytokines, such as TNF and IL-1, may play in this process has now been well accepted, but the extent of the reprogramming of the transcriptional machinery initiated by these factors remains to be fully appreciated. With the advent of microarray technology, a more comprehensive analysis of this process is now available. In this report we review data obtained with this technology to provide an overview of the extent of changes induced in astrocytes by the cytokine IL-1.

Gene Expression in Temporal Lobe Epilepsy is Consistent with Increased Release of Glutamate by Astrocytes

“…Astrocytes are known to contribute to the inflammatory environment of the central nervous system by producing a wide range of immunologically relevant molecules (49,50). Among these are class II major histocompatibility complex antigens (49) HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1, and HLA-DRB3 which were up-regulated in this study.…”

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

“…IL-1β can induce gliosis in vivo and in vitro. Stimulation of astrocytes with IL-1β leads to up-regulation or synthesis of several of the genes known to be regulated in reactive glia [27]. Our previous investigation demonstrated apelin stimulated Müller proliferation and migration, and induced gliosis of Müller in diabetic retinopathy [7,28,29].…”

Astrocytes and Epilepsy

“…In vivo and in vitro studies have shown that astrocytes can produce a range of immunologically relevant molecules, including class II major histocompatibility complex antigens, many cytokines, and chemokines, such as those seen in the sclerotic hippocampus. 53,54 Immunohistochemical analysis of sclerotic hippocampi from TLE patients has revealed increased expression of the NFkB-p65 subunit in astrocytes. 55 Several genes regulated through the NFkB pathway are among those up-regulated in the sclerotic hippocampus (S100B, ezrin/radixin/moesin, the chemokines [CCL2, CCL3, CCL4, CXCL1, and the chemokine receptor CXCR4]).…”

“…Factors such as IL-1␤ is shown to be able through binding to IL receptors on astrocytes activate them to produce several of the factors observed in micro-array studies to be regulated in astrocytes. 54 Many of these are transcribed by the transcription factor NFkB, and the resultant molecules may be involved in several functions, such as changing astrocyte morphology (GFAP, vimentin, Ezrin, Radixin, Moesin), triggering intracellular Ca 2ϩ release (S100B, CXCR4, COX2/PGE2 pathway), and influencing the functioning of the microvasculature (CCL2, CCL3, EPOR) and down regulating critical membrane channels and transporters (Kir 4.1, AQP4). 50 Components of the complement cascade increase vascular permeability.…”