Abstract
Cytokines play a major role in the initiation, propagation, regulation and suppression of inflammatory responses [1–3]. Most cells do not constitutively express cytokines, but rather an activation event results in cytokine gene transcription. The major intrinsic sources of cytokines in the brain are glial cells [1>]. However, elements of the brain vasculature including cerebral endothelial cells (CEC), pericytes, and perivascular macrophages, as well as peripheral immune cells that infiltrate the brain in pathological states, are significant sources of cytokines [1–4].
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References
Benveniste ET (1997) Cytokine expression in the nervous system. In: RW Keane, WF Hickey (eds): Immunology of the nervous system. Oxford University Press, New York, Oxford, 419–460
Dinarello CA (1998) Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 16: 457–499
Stanimirovic D and Satoh K (2000) Inflammatory mediators of cerebral endothelium: A role in ischemic brain inflammation. Brain Pathol 10: 113–126
Feuerstein GZ, Wang X, Barone FC (1998) The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation 5: 143–159
Hill JK, Gunion-Rinker L, Kulhanek D, Lessov N, Kim S, Clark WM, Dixon MP, Nishi R, Stenzel-Poore MP, Eckenstein FP (1999) Temporal modulation of cytokine expression following focal cerebral ischemia in mice. Brain Res 820: 45–54
Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mam-malian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Rev 28: 370–490
Hughes PE, Alexi T, Walton M, Williams CE, Dragunow M, Clark RG, Gluckman PD (1999) Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system. Prog Neurobiol 57: 421–450
Semenza GL (2000) Expression of hypoxia-inducible factor 1: mechanisms and conse-quences. Biochem Pharmacol 59: 47–53
Ratcliffe PJ, O’Rourke JF, Maxwell PH, Pugh CW (1998) Oxygen sensing, hypoxiainducible factor-1 and the regulation of mammalian gene expression. J Exp Biol 201: 1153–1162
Bergeron M, Yu AY, Solway KE, Semenza GL, Sharp FR (1999) Induction of hypoxiainducible factor-1 (HIF-1) and its target genes following focal ischemia in rat brain. Eur J Neurosci 11: 4159–4170
Stephenson D, Yin T, Smalstig EB, Hsu MA, Panetta J, Little S, Clemens J (2000) Tran-scription factor nuclear factor-kappa B is activated in neurons after focal cerebral ischemia. J Cereb Blood Flow Metab 20: 592–603
Salminen A, Liu PK, Hsu CY (1995) Alteration of transcription factor binding activities in the ischemic rat brain. Biochem Biophys Res Comm 212: 932–944
Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T (1995) Transcriptional regulation of endothelial cell adhesion molecules: NF-κB and cytokine-inducible enhancers. FASEB J 9: 899–909
Novotny V, Prieschl EE, Csonga R, Fabjani G, Baumruker T (1998) Nrfl in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells. Nucleic Acids Res 26: 5480–5485
Grilli M, Memo M (1999) Nuclear factor-kappaB/Rel proteins: a point of convergence of signalling pathways relevant in neuronal function and dysfunction. Biochem Pharmacol 57: 1–7
Baldwin Jr AS (1996) The NF-κB and IκB proteins: New discoveries and insights. Ann Rev Immunol 14: 649–681
Grisham MB, Palombella VJ, Elliott PJ, Conner EM, Brand S, Wong HL, Pien C, Mazzola LM, Destree A, Parent L, Adams J (1997) Inhibition of NF-κB activation in vitro and in vivo: role of 26S proteasome. Methods in Enzymology 300: 345–363
Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EBM, Mueller-Diekmann C, Farahifar D, Baeuerle PA, Peyron J-F (1996) Tyrosine phosphorylation of IκB-α activates NF-κB without proteolytic degradation of IκB-α. Cell 86: 787–798
Wenger RH (2000) Mammalian oxygen sensing, signalling and gene regulation. J Exp Biol 203: 1253–1263
Haddad JJ, Olver RE, Land SC (2000) Antioxidant/pro-oxidant equilibrium regulates HIF-1(alpha) and NF-(kappa)B redox sensitivity: Evidence for inhibition by glutathione oxidation in alveolar epithelial cells. J Biol Chem 275: 21130–21139.
Kallio PJ, Wilson WJ, O’Brien S, Makino Y, Poellinger L (1999) Regulation of the hypoxia-inducible transcription factor la by the ubiquitin-proteasome pathway. J Biol Chem 274: 6519–6525
Stanimirovic D, Zhang W, Howlett C, Lemieux P, Smith C (2000) Inflammatory gene transcription in human astrocytes exposed to hypoxia: Role of NF-κB and autocrine stimulation. J Neuroimmunol; in press
Zhang W, Smith C, Stanimirovic DB (2000) Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1β. J Cerebral Blood Flow Metab 20: 967–978
Zhang W, Howlett C, Mojsilovic-Petrovic J, Carmeliet P, Stanimirovic D (2000) Evidence that interleukin converting enzyme (ICE) and interleukin-1β (IL-1β) are transcriptionally regulated by the hypoxia-inducible factor-1 (HIF-1) in human astrocytes and brain endothelial cells exposed to hypoxia. J Biol Chem; submitted
Auron PE (1998) The interleukin-1 receptor: Ligand interactions and signal transduction. Cytokine and Growth Factors Reviews 9: 221–237
Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (1999) Signaling by proinflam-matory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 13: 1297–308
Sizemore N, Leung S, Stark GR (1999) Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/Re1A subunit. Mol Cell Biol 19: 4798–4805
Clerk A, Harrison JG, Long CS, Sugden PH (1999) Pro-inflammatory cytokines stimulate mitogen-activated protein kinase subfamilies, increase phosphorylation of c-Jun and ATF2 and upregulate c-Jun protein in neonatal rat ventricular myocytes. J Mol Cell Cardiol 31: 2087–1099
Loddick SA, Wong ML, Bongiorno PB, Gold PW, Licinio J, Rothwell NJ (1997) Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun 234: 211–215
Ye K, Koch KC, Clark BD, Dinarello CA (1992) Interleukin-1 down-regulates gene and surface expression of interleukin-1 receptor type I by destabilising mRNA whereas interleukin-2 increases its expression. Immunology 75: 427–434
Zhang W, Smith C, Monette R, Shapiro A, Hutchison J, Stanimirovic D (1999) Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J Neuroimmunol 101: 148–160
Young P (1998) Pharmacological modulation of cytokine action and production through signaling pathways. Cytokine and Growth Factors Reviews 9: 239–257
Buchan AM, Li H, Blackburn B (2000) Neuroprotection achieved with a novel proteasome inhibitor which blocks NF-kappaB activation. Neuroreport 11: 427–430
Tomita N, Morishita R, Tomita S, Yamamoto K, Aoki M, Matsushita H, Hayashi S, Higaki J, Ogihara T (1998) Transcription factor decoy for nuclear factor-κB inhibits tumor-necrosis factor-a-induced expression of interleukin-6 and intracellular adhesion molecule-1 in endothelial cells. J Hypertension 16: 993–1000
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Stanimirovic, D.B. (2001). Inflammatory activation of brain cells by hypoxia: transcription factors and signaling pathways. In: Feuerstein, G.Z. (eds) Inflammation and Stroke. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8297-2_9
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DOI: https://doi.org/10.1007/978-3-0348-8297-2_9
Publisher Name: Birkhäuser, Basel
Print ISBN: 978-3-0348-9508-8
Online ISBN: 978-3-0348-8297-2
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