Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes respond vigorously to diverse neurological insults. It is still not clear, however, whether this response is stereotypic following different insults or varies according to the injury. We have used a novel immunocytochemical marker of reactive astrocytes, termed M22, together with antibodies to glial fibrillary acidic protein (GFAP), to analyze region- and insult-specific differences in reactive astrocytosis in the murine central nervous system (CNS). Pathology was variously induced by (1) infectious agents, (2) transgenic overexpression of a viral glycoprotein or cytokine, or (3) focal trauma. Scrapie infection induced high levels of both GFAP and M22 epitope expression by hippocampal reactive astrocytes, but neither scrapie nor wild mouse retrovirus infection induced detectable M22 staining in reactive astrocytes of the caudal brain. Focal trauma and human immunodeficiency virus gp120 overexpression induced M22 expression only in the hippocampus, while interleukin-6 overexpression induced it in cerebellar astrocytes. Although M22 expression was limited to areas with extensive damage, GFAP expression was induced in every region of the mouse brain displaying pathology. Staining of routinely fixed human brain tissue demonstrated that M22 also labeled reactive astrocytes in chronic human CNS disease. The restriction of M22 expression to areas of strongly GFAP-positive astrocytosis suggests that the M22 antibody identified highly activated reactive astrocytes. Because of this selective staining of activated astrocytes, the M22 antibody may provide neuropathologists with a good marker for qualitative analysis of the astrocytic response to different injuries.
 ...
PMID:The M22 antibody identifies highly activated reactive astrocytes responding to central nervous system disease. 883 43

In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs) of the spleen and lymph nodes are important sites of extraneural replication, from which infection is likely to spread to the CNS along peripheral nerves. Here, using immunodeficient mice, we investigate the identity of the cells in the spleen that are important for disease propagation. Despite possessing functional T and B lymphocytes, tumor necrosis factor alpha-deficient (TNF-alpha(-/-)) mice lack GCs and follicular dendritic cell (FDC) networks in lymphoid tissues. In contrast, lymphoid tissues of interleukin-6-deficient (IL-6(-/-)) mice possess FDC networks but have impaired GCs. When the CNSs of TNF-alpha(-/-), IL-6(-/-), and wild-type mice were directly challenged with the ME7 scrapie strain, 100% of the mice were susceptible, developing disease after closely similar incubation periods. However, when challenged peripherally (intraperitoneally), most TNF-alpha(-/-) mice failed to develop scrapie up to 503 days postinjection. All wild-type and IL-6(-/-) mice succumbed to disease approximately 300 days after the peripheral challenge. High levels of scrapie infection and the disease-specific isomer of the prion protein, PrP(Sc), were detectable in spleens from challenged wild-type and IL-6(-/-) mice but not from TNF-alpha(-/-) mice. Histopathological analysis of spleen tissue demonstrated heavy PrP accumulations in direct association with FDCs in challenged wild-type and IL-6(-/-) mice. No PrP(Sc) accumulation was detected in spleens from TNF-alpha(-/-) mice. We conclude that, for the ME7 scrapie strain, mature FDCs are critical for replication in lymphoid tissues and that in their absence, neuroinvasion following peripheral challenge is impaired.
 ...
PMID:Tumor necrosis factor alpha-deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie. 1070 51

Previous studies have demonstrated a role for microglia in the neuronal loss that occurs in the transmissible spongiform encephalopathies or prion diseases. In the present studies, the processes that lead to the death of neurones treated with synthetic peptides derived from the prion protein (PrP) were fully activated within 1 h, although neuronal cell death was not seen until 24 h later. Similarly, neurones exposed to PrP peptides for only 1 h activated microglia and a temporal relationship between the production of interleukin-6, an indicator of microglial activation, and microglial killing of PrP-treated neurones was also demonstrated. Activation of microglia and microglia-mediated killing of PrP-treated neurones or scrapie-infected neuroblastoma cells were maximal only when microglia were in direct contact with neurones.
 ...
PMID:Temporal and spatial relationship between the death of PrP-damaged neurones and microglial activation. 1235 29

In the present study the accumulation of protease resistant prion protein (PrPres) in scrapie-infected neuroblastoma cells (ScN2a cells) was shown to be dependent on culture conditions. The highest levels of PrPres were found in slow growing cells. Further increases in PrPres accumulation were observed in ScN2a cells treated with retinoic acid, a compound that is associated with neuronal differentiation. The effects of retinoic acid were dose-dependent with a maximal effect at 200 ng/ml. A similar increase in PrPres was observed in another prion-infected cell line, scrapie-mouse brain (SMB) cells, treated with retinoic acid while retinoic acid increased the amount of PrPC in non-infected cells. Other drugs reported to cause neuronal differentiation, such as phorbol esters, did not increase the PrPres content of ScN2a cells. The survival of retinoic acid-treated ScN2a cells co-cultured with microglia was significantly reduced when compared to untreated ScN2a cells and an inverse correlation was demonstrated between the PrPres content of cells and their survival when co-cultured with microglia. The production of interleukin-6 by microglia cultured with retinoic acid-treated ScN2a cells was significantly higher than that of microglia cultured with untreated ScN2a cells.
 ...
PMID:Manipulation of PrPres production in scrapie-infected neuroblastoma cells. 1532 30