Top

Published in:

Open Access 01-12-2011 | Research

Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats

Authors: Maria Cristina Guerra, Lucas S Tortorelli, Fabiana Galland, Carollina Da Ré, Elisa Negri, Douglas S Engelke, Letícia Rodrigues, Marina C Leite, Carlos-Alberto Gonçalves

Published in: Journal of Neuroinflammation | Issue 1/2011

Abstract

Background

Inflammatory responses in brain are primarily mediated by microglia, but growing evidence suggests a crucial importance of astrocytes. S100B, a calcium-binding protein secreted by astrocytes, has properties of a neurotrophic or an inflammatory cytokine. However, it is not known whether primary signals occurring during induction of an inflammatory response (e.g. lipopolysaccharide, LPS) directly modulate S100B.

Methods

In this work, we evaluated whether S100B levels in cerebrospinal fluid (CSF) and serum of Wistar rats are affected by LPS administered by intraperitoneal (IP) or intracerebroventricular (ICV) injection, as well as whether primary astrocyte cultures respond directly to lipopolysaccharide.

Results

Our data suggest that S100B secretion in brain tissue is stimulated rapidly and persistently (for at least 24 h) by ICV LPS administration. This increase in CSF S100B was transient when LPS was IP administered. In contrast to these S100B results, we observed an increase in in TNFα levels in serum, but not in CSF, after IP administration of LPS. In isolated astrocytes and in acute hippocampal slices, we observed a direct stimulation of S100B secretion by LPS at a concentration of 10 μg/mL. An involvement of TLR4 was confirmed by use of specific inhibitors. However, lower levels of LPS in astrocyte cultures were able to induce a decrease in S100B secretion after 24 h, without significant change in intracellular content of S100B. In addition, after 24 h exposure to LPS, we observed a decrease in astrocytic glutathione and an increase in astrocytic glial fibrillary acidic protein.

Conclusions

Together, these data contribute to the understanding of the effects of LPS on astrocytes, particularly on S100B secretion, and help us to interpret cerebrospinal fluid and serum changes for this protein in neuroinflammatory diseases. Moreover, non-brain S100B-expressing tissues may be differentially regulated, since LPS administration did not lead to increased serum levels of S100B.

Available only for authorised users

Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, Tubaro C, Giambanco I: S100B's double life: intracellular regulator and extracellular signal. Biochim Biophys Acta. 2009, 1793: 1008-1022. 10.1016/j.bbamcr.2008.11.009.CrossRefPubMed

Pinto SS, Gottfried C, Mendez A, Goncalves D, Karl J, Goncalves CA, Wofchuk S, Rodnight R: Immunocontent and secretion of S100B in astrocyte cultures from different brain regions in relation to morphology. FEBS Lett. 2000, 486: 203-207. 10.1016/S0014-5793(00)02301-2.CrossRefPubMed

Tramontina AC, Tramontina F, Bobermin LD, Zanotto C, Souza DF, Leite MC, Nardin P, Gottfried C, Goncalves CA: Secretion of S100B, an astrocyte-derived neurotrophic protein, is stimulated by fluoxetine via a mechanism independent of serotonin. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32: 1580-1583. 10.1016/j.pnpbp.2008.06.001.CrossRefPubMed

Sakatani S, Seto-Ohshima A, Shinohara Y, Yamamoto Y, Yamamoto H, Itohara S, Hirase H: Neural-activity-dependent release of S100B from astrocytes enhances kainate-induced gamma oscillations in vivo. J Neurosci. 2008, 28: 10928-10936. 10.1523/JNEUROSCI.3693-08.2008.CrossRefPubMed

Buyukuysal RL: Protein S100B release from rat brain slices during and after ischemia: comparison with lactate dehydrogenase leakage. Neurochem Int. 2005, 47: 580-588. 10.1016/j.neuint.2005.06.009.CrossRefPubMed

Nardin P, Tramontina F, Leite MC, Tramontina AC, Quincozes-Santos A, de Almeida LM, Battastini AM, Gottfried C, Goncalves CA: S100B content and secretion decrease in astrocytes cultured in high-glucose medium. Neurochem Int. 2007, 50: 774-782. 10.1016/j.neuint.2007.01.013.CrossRefPubMed

Leite MC, Brolese G, de Almeida LM, Pinero CC, Gottfried C, Goncalves CA: Ammonia-induced alteration in S100B secretion in astrocytes is not reverted by creatine addition. Brain Res Bull. 2006, 70: 179-185. 10.1016/j.brainresbull.2006.05.003.CrossRefPubMed

Steiner J, Bernstein HG, Bielau H, Berndt A, Brisch R, Mawrin C, Keilhoff G, Bogerts B: Evidence for a wide extra-astrocytic distribution of S100B in human brain. BMC Neurosci. 2007, 8: 2-10.1186/1471-2202-8-2.PubMedCentralCrossRefPubMed

Haimoto H, Kato K, Suzuki F, Nagura H: The ultrastructural changes of S-100 protein localization during lipolysis in adipocytes. An immunoelectron-microscopic study. Am J Pathol. 1985, 121: 185-191.PubMedCentralPubMed

10.

Rothermundt M, Peters M, Prehn JH, Arolt V: S100B in brain damage and neurodegeneration. Microsc Res Tech. 2003, 60: 614-632. 10.1002/jemt.10303.CrossRefPubMed

11.

Sen J, Belli A: S100B in neuropathologic states: the CRP of the brain?. J Neurosci Res. 2007, 85: 1373-1380. 10.1002/jnr.21211.CrossRefPubMed

12.

de Souza DF, Leite MC, Quincozes-Santos A, Nardin P, Tortorelli LS, Rigo MM, Gottfried C, Leal RB, Goncalves CA: S100B secretion is stimulated by IL-1beta in glial cultures and hippocampal slices of rats: Likely involvement of MAPK pathway. J Neuroimmunol. 2009, 206: 52-57. 10.1016/j.jneuroim.2008.10.012.CrossRefPubMed

13.

Kim SH, Smith CJ, Van Eldik LJ: Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production. Neurobiol Aging. 2004, 25: 431-439. 10.1016/S0197-4580(03)00126-X.CrossRefPubMed

14.

Bianchi R, Giambanco I, Donato R: S100B/RAGE-dependent activation of microglia via NF-kappaB and AP-1 Co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging. 2010, 31: 665-677. 10.1016/j.neurobiolaging.2008.05.017.CrossRefPubMed

15.

Ponath G, Schettler C, Kaestner F, Voigt B, Wentker D, Arolt V, Rothermundt M: Autocrine S100B effects on astrocytes are mediated via RAGE. J Neuroimmunol. 2007, 184: 214-222. 10.1016/j.jneuroim.2006.12.011.CrossRefPubMed

16.

Belanger M, Magistretti PJ: The role of astroglia in neuroprotection. Dialogues Clin Neurosci. 2009, 11: 281-295.PubMedCentralPubMed

17.

Eng LF, Ghirnikar RS, Lee YL: Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res. 2000, 25: 1439-1451. 10.1023/A:1007677003387.CrossRefPubMed

18.

Hauss-Wegrzyniak B, Lukovic L, Bigaud M, Stoeckel ME: Brain inflammatory response induced by intracerebroventricular infusion of lipopolysaccharide: an immunohistochemical study. Brain Res. 1998, 794: 211-224. 10.1016/S0006-8993(98)00227-3.CrossRefPubMed

19.

Farina C, Aloisi F, Meinl E: Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007, 28: 138-145. 10.1016/j.it.2007.01.005.CrossRefPubMed

20.

Carpentier PA, Duncan DS, Miller SD: Glial toll-like receptor signaling in central nervous system infection and autoimmunity. Brain Behav Immun. 2008, 22: 140-147. 10.1016/j.bbi.2007.08.011.PubMedCentralCrossRefPubMed

21.

Liao CK, Wang SM, Chen YL, Wang HS, Wu JC: Lipopolysaccharide-induced inhibition of connexin43 gap junction communication in astrocytes is mediated by downregulation of caveolin-3. Int J Biochem Cell Biol. 2010, 42: 762-770. 10.1016/j.biocel.2010.01.016.CrossRefPubMed

22.

Vergara D, Martignago R, Bonsegna S, De Nuccio F, Santino A, Nicolardi G, Maffia M: IFN-beta reverses the lipopolysaccharide-induced proteome modifications in treated astrocytes. J Neuroimmunol. 2010, 221: 115-120. 10.1016/j.jneuroim.2010.01.002.CrossRefPubMed

23.

Brahmachari S, Fung YK, Pahan K: Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J Neurosci. 2006, 26: 4930-4939. 10.1523/JNEUROSCI.5480-05.2006.PubMedCentralCrossRefPubMed

24.

Leite MC, Galland F, de Souza DF, Guerra MC, Bobermin L, Biasibetti R, Gottfried C, Goncalves CA: Gap junction inhibitors modulate S100B secretion in astrocyte cultures and acute hippocampal slices. J Neurosci Res. 2009

25.

Rodrigues L, Biasibetti R, Swarowsky A, Leite MC, Quincozes-Santos A, Quilfeldt JA, Achaval M, Goncalves CA: Hippocampal alterations in rats submitted to streptozotocin-induced dementia model are prevented by aminoguanidine. J Alzheimers Dis. 2009, 17: 193-202.PubMed

26.

Gottfried C, Valentim L, Salbego C, Karl J, Wofchuk ST, Rodnight R: Regulation of protein phosphorylation in astrocyte cultures by external calcium ions: specific effects on the phosphorylation of glial fibrillary acidic protein (GFAP), vimentin and heat shock protein 27 (HSP27). Brain Res. 1999, 833: 142-149. 10.1016/S0006-8993(99)01503-6.CrossRefPubMed

27.

Nardin P, Tortorelli L, Quincozes-Santos A, de Almeida LM, Leite MC, Thomazi AP, Gottfried C, Wofchuk ST, Donato R, Goncalves CA: S100B Secretion in Acute Brain Slices: Modulation by Extracellular Levels of Ca(2+) and K (+). Neurochem Res. 2009

28.

Leite MC, Galland F, Brolese G, Guerra MC, Bortolotto JW, Freitas R, Almeida LM, Gottfried C, Goncalves CA: A simple, sensitive and widely applicable ELISA for S100B: Methodological features of the measurement of this glial protein. J Neurosci Methods. 2008, 169: 93-99. 10.1016/j.jneumeth.2007.11.021.CrossRefPubMed

29.

Tramontina F, Leite MC, Cereser K, de Souza DF, Tramontina AC, Nardin P, Andreazza AC, Gottfried C, Kapczinski F, Goncalves CA: Immunoassay for glial fibrillary acidic protein: antigen recognition is affected by its phosphorylation state. J Neurosci Methods. 2007, 162: 282-286. 10.1016/j.jneumeth.2007.01.001.CrossRefPubMed

30.

Browne RW, Armstrong D: Reduced glutathione and glutathione disulfide. Methods Mol Biol. 1998, 108: 347-352.PubMed

31.

Goncalves CA, Concli Leite M, Nardin P: Biological and methodological features of the measurement of S100B, a putative marker of brain injury. Clin Biochem. 2008, 41: 755-763. 10.1016/j.clinbiochem.2008.04.003.CrossRefPubMed

32.

Garnier Y, Berger R, Alm S, von Duering MU, Coumans AB, Michetti F, Bruschettini M, Lituania M, Hasaart TH, Gazzolo D: Systemic endotoxin administration results in increased S100B protein blood levels and periventricular brain white matter injury in the preterm fetal sheep. Eur J Obstet Gynecol Reprod Biol. 2006, 124: 15-22. 10.1016/j.ejogrb.2005.05.014.CrossRefPubMed

33.

Rosengarten B, Wolff S, Klatt S, Schermuly RT: Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model. Crit Care. 2009, 13: R139-10.1186/cc8020.PubMedCentralCrossRefPubMed

34.

van den Boogaard M, Ramakers BP, van Alfen N, van der Werf SP, Fick WF, Hoedemaekers CW, Verbeek MM, Schoonhoven L, van der Hoeven JG, Pickkers P: Endotoxemia-induced inflammation and the effect on the human brain. Crit Care. 2010, 14: R81-10.1186/cc9001.PubMedCentralCrossRefPubMed

35.

Gorina R, Font-Nieves M, Marquez-Kisinousky L, Santalucia T, Planas AM: Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia. 2011, 59: 242-255. 10.1002/glia.21094.CrossRefPubMed

36.

Banks WA, Robinson SM: Minimal penetration of lipopolysaccharide across the murine blood-brain barrier. Brain Behav Immun. 2010, 24: 102-109. 10.1016/j.bbi.2009.09.001.PubMedCentralCrossRefPubMed

37.

Edwards MM, Robinson SR: TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer's disease. J Neural Transm. 2006, 113: 1709-1715. 10.1007/s00702-006-0479-5.CrossRefPubMed

38.

Leite M, Frizzo JK, Nardin P, de Almeida LM, Tramontina F, Gottfried C, Goncalves CA: Beta-hydroxy-butyrate alters the extracellular content of S100B in astrocyte cultures. Brain Res Bull. 2004, 64: 139-143. 10.1016/j.brainresbull.2004.06.005.CrossRefPubMed

39.

Sheng JG, Ito K, Skinner RD, Mrak RE, Rovnaghi CR, Van Eldik LJ, Griffin WS: In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis. Neurobiol Aging. 1996, 17: 761-766. 10.1016/0197-4580(96)00104-2.PubMedCentralCrossRefPubMed

40.

Hinkle DA, Harney JP, Cai A, Hilt DC, Yarowsky PJ, Wise PM: Basic fibroblast growth factor-2 and interleukin-1 beta regulate S100 beta expression in cultured astrocytes. Neuroscience. 1998, 82: 33-41.CrossRefPubMed

41.

Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn AP, Mori T, Gotz M: Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci USA. 2008, 105: 3581-3586. 10.1073/pnas.0709002105.PubMedCentralCrossRefPubMed

42.

Dringen R, Hirrlinger J: Glutathione pathways in the brain. Biol Chem. 2003, 384: 505-516. 10.1515/BC.2003.059.CrossRefPubMed

43.

Liu L, Li Y, Van Eldik LJ, Griffin WS, Barger SW: S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors. J Neurochem. 2005, 92: 546-553. 10.1111/j.1471-4159.2004.02909.x.CrossRefPubMed

44.

Bianchi ME: DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007, 81: 1-5.CrossRefPubMed

45.

Peri F, Piazza M, Calabrese V, Damore G, Cighetti R: Exploring the LPS/TLR4 signal pathway with small molecules. Biochem Soc Trans. 2010, 38: 1390-1395. 10.1042/BST0381390.CrossRefPubMed

46.

Goncalves CA, Leite MC, Guerra MC: Adipocytes as an Important Source of Serum S100B and Possible Roles of This Protein in Adipose Tissue. Cardiovasc Psychiatry Neurol. 2010, 2010: 790431.PubMedCentralPubMed

47.

Cirillo C, Sarnelli G, Esposito G, Grosso M, Petruzzelli R, Izzo P, Cali G, D'Armiento FP, Rocco A, Nardone G, et al: Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein. Neurogastroenterol Motil. 2009, 21: 1209-e1112. 10.1111/j.1365-2982.2009.01346.x.CrossRefPubMed

48.

Unden J, Christensson B, Bellner J, Alling C, Romner B: Serum S100B levels in patients with cerebral and extracerebral infectious disease. Scand J Infect Dis. 2004, 36: 10-13. 10.1080/00365540310017294.CrossRefPubMed

Title: Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats
Authors: Maria Cristina Guerra
Lucas S Tortorelli
Fabiana Galland
Carollina Da Ré
Elisa Negri
Douglas S Engelke
Letícia Rodrigues
Marina C Leite
Carlos-Alberto Gonçalves
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-8-128

At a glance: The STEP trials

Springer Medicine

Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2011

Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during Experimental Autoimmune Encephalomyelitis

Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study

Fingolimod modulates microglial activation to augment markers of remyelination

Neuro-inflammation, blood-brain barrier, seizures and autism

HIV-1 Tat activates indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures in a p38 mitogen-activated protein kinase-dependent manner

Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures