Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation

Bates, Stewart; Read, Simon; Harrison, David; Topp, Simon; Morrow, Rachel; Gale, Davina; Murdock, Paul R.; Barone, Frank C.; Parsons, Andrew A.; Gloger, Israel

doi:10.1016/s0169-328x(01)00186-3

Cited by 36 publications

(15 citation statements)

References 52 publications

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“…Lipocortin-1 possesses anti-inflammatory effects probably through inhibition of phospholipase A2, and is proposed to be an endogenous neuroprotective molecule in a number of tissues including the brain (Rothwell and Relton, 1993). An early 10-fold increase of SOCS-3 (but not SOCS-5) was found in the immature brain, which basically agrees with the response to ischemia in the adult brain (Bates et al, 2001). This suppressor of cytokine signaling is induced by interleukin-6, interleukin-10, and interferon-␥, and may exert its antiinflammatory effect through inhibition of JAK2 kinase (Larsen and Ropke, 2002).…”

Section: Anti-inflammatory Cytokines or Receptorssupporting

confidence: 82%

Inflammatory Gene Profiling in the Developing Mouse Brain after Hypoxia-Ischemia

Hedtjärn¹,

Mallard²,

Hagberg

2004

J Cereb Blood Flow Metab

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Summary:Brain ischemia triggers an inflammatory reaction that progresses for days to weeks and seems to have a role in secondary progression of injury. Inflammation induces a complex pattern of signaling molecules with partly contradictory actions, and the responses may be different in the immature and adult brain. The authors characterized the global inflammatory gene expression in the developing brain as a first step toward understanding the protective and deleterious effects of inflammation after hypoxia-ischemia. Oligonucleotide arrays were used to investigate inflammatory genes in cortex, hippocampus, thalamus, and striatum at 2, 8, 24, and 72 hours after hypoxiaischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia. After hypoxia-ischemia, 148 inflammatory genes were differentially expressed. More than 97% of the genes were upregulated and 93% had not previously been reported after hypoxia-ischemia in the immature brain. The results indicate that microglia/macrophages, Tand B-cells, NK-cells, mast cells, dendritic cells, and polymorphonuclear leukocytes may participate in the response to hypoxia-ischemia. In addition, novel cytokines/chemokines, complement-related, interferon-regulated, components of the TIR/nuclear factor-B pathway, and a number of immunomodulatory genes were induced. Several of these genes may be of pathophysiologic significance after neonatal hypoxiaischemia.

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Section: Anti-inflammatory Cytokines or Receptorssupporting

confidence: 82%

Inflammatory Gene Profiling in the Developing Mouse Brain after Hypoxia-Ischemia

Hedtjärn¹,

Mallard²,

Hagberg

2004

J Cereb Blood Flow Metab

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“…Unfortunately, the functional importance of SOCS3 expression in these models was not studied. In addition, SOCS3 expression is upregulated after middle cerebral-artery occlusion (MCAO) in the rat [62,63]. Infusion of antisense SOCS3 into the ventricle before MCAO increases lesion volumes and worsens neurological outcomes compared with control-infused mice [62], suggesting that upregulation of SOCS3 in this model of stroke is neuroprotective.…”

Section: Socs3 In Traumatic Brain and Spinal Cord Insultsmentioning

confidence: 99%

SOCS1 and SOCS3 in the control of CNS immunity

Baker

Akhtar

Benveniste

2009

Trends in Immunology

229

203

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In the decade following their initial discovery, the suppressor of cytokine signaling (SOCS) proteins have been studied for their potential use as immunomodulators in disease. SOCS proteins, especially SOCS1 and SOCS3, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS, including inflammatory cytokine and chemokine production, activation of microglia, macrophages and astrocytes, immune cell infiltration and autoimmunity. We describe CNS-relevant in vitro and in vivo studies that have examined the function of SOCS1 or SOCS3 under various neuroinflammatory or neuropathological conditions, including exposure of CNS cells to inflammatory cytokines or bacterial infection, demyelinating insults, stroke, spinal cord injury, multiple sclerosis and glioblastoma multiforme. The SOCS familySuppressor of cytokine signaling (SOCS) proteins are intracellular, cytokine-inducible proteins that inhibit cytokine signaling in numerous cell types, including cells of the immune and central nervous systems (CNS). The SOCS family is composed of eight members: cytokine inducible SRC homology 2 (SH2)-domain-containing protein (CIS) and SOCS1 to SOCS7 [1,2]. To exert their function, SOCS proteins associate with phosphorylated tyrosine residues on Janus kinases (JAKs) and/or cytokine receptor subunits through a central SH2 domain. A C-terminal SOCS box then interacts with components of the ubiquitin ligase machinery and mediates proteosomal degradation of associated proteins [3]. In addition, the N-terminus of SOCS1 and SOCS3, specifically, contains a kinase-inhibitory region (KIR) (Figure 1), which acts as a pseudosubstrate for JAKs, conferring inhibition of JAK kinase activity [1]. Through these interactions, SOCS proteins attenuate responses to cytokines and growth factors. Because studies of SOCS family members have established SOCS1 and SOCS3 as the most important in regulating innate and adaptive immune responses, they are the focus of this review. There is limited information regarding the role of other SOCS family members in CNS immunity. Therefore, they are not discussed here. SOCS regulation of JAK/STAT signalingSignal transduction through the JAK/signal transducer and activator of transcription (STAT) signaling pathway is a crucial mediator of inflammatory and immune responses in the CNS [4]. Activation of the JAK/STAT pathway is achieved by cytokines binding to their associated cell-surface receptors, leading to a series of phosphorylation events, culminating in phosphorylation of the STAT transcription factors (Figure 2). Activated STATs promote Corresponding author: Benveniste, E.N. (tika@uab.edu). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Plea...

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“…MCP-1 is expressed in ipsilateral cortex and striatum after MCAO in rats [57, 61] beginning 12 h after ischemia in neurons and 2 days after ischemia in astrocytes [62]. MCP-1 deficiency is protective in a mouse stroke model, probably because of IL1-β in ischemic tissue [63].…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%