Skip to main content
Erschienen in: Inflammation Research 4/2011

01.04.2011 | Original Research Paper

Apolipoprotein(a) inhibits lipopolysaccharide-induced IL-6 secretion in human astrocytoma cell line by interfering with lipopolysaccharide signaling

verfasst von: Guglielmina Chimienti, Anna Mezzapesa, Grazia M. Liuzzi, Tiziana Latronico, Gabriella Pepe

Erschienen in: Inflammation Research | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

Abstract

Objective

To examine the role of lipoprotein(a) [Lp(a)] on the inflammatory response of cells in the nervous system by investigating its effect on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion.

Materials and methods

Human astrocytoma U373 cells were treated with recombinant apolipoprotein(a) [r-apo(a)] A10K (175–11 nM), alone or in combination with LPS (100 and 10 ng/ml). IL-6 levels were evaluated by immunoblotting. Statistical analysis was performed by one-way ANOVA.

Results

r-apo(a) caused dose-dependent inhibition of LPS-induced IL-6 secretion (100 ng/ml LPS, p = 0.0205; 10 ng/ml LPS, p = 0.0005). Pre-treatment of cells with 88 nM r-apo(a), rinsing, and activation with 10 ng/ml LPS did not reverse the inhibition (p = 0.0048), which could be reversed by supplementation with excess serum (5–20%) (p = 0.0454) or recombinant CD14 (2.0–0.05 μg/ml) (p = 0.0230).

Conclusions

Our data indicate that apo(a) plays a natural anti-endotoxin role which relies on its interference with cell-associated and serum components of LPS signaling.
Literatur
1.
Zurück zum Zitat Utermann G. Lipoprotein(a). In: Scriver CR, Baudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited diseases. New York: McGraw-Hill; 1995. p. 1887–912. Utermann G. Lipoprotein(a). In: Scriver CR, Baudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited diseases. New York: McGraw-Hill; 1995. p. 1887–912.
2.
Zurück zum Zitat de la Peña-Diaz A, Izaguirre-Avila R, Anglés-Cano E. Lipoprotein Lp(a) and atherothrombotic disease. Arch Med Res. 2000;31:353–9.PubMedCrossRef de la Peña-Diaz A, Izaguirre-Avila R, Anglés-Cano E. Lipoprotein Lp(a) and atherothrombotic disease. Arch Med Res. 2000;31:353–9.PubMedCrossRef
3.
Zurück zum Zitat Chimienti G, Lamanuzzi BL, Nardulli M, Colacicco AM, Capurso A, La Gioia R, et al. Apo(a) variants and lipoprotein(a) in men with or without myocardial infarction. Exp Mol Pathol. 2002;73:28–34.PubMedCrossRef Chimienti G, Lamanuzzi BL, Nardulli M, Colacicco AM, Capurso A, La Gioia R, et al. Apo(a) variants and lipoprotein(a) in men with or without myocardial infarction. Exp Mol Pathol. 2002;73:28–34.PubMedCrossRef
4.
Zurück zum Zitat Dieplinger B, Lingenhel A, Baumgartner N, Poelz W, Dieplinger H, Haltmayer M, et al. Increased serum lipoprotein(a) concentrations and low molecular weight phenotypes of apolipoprotein(a) are associated with symptomatic peripheral arterial disease. Clin Chem. 2007;53:1298–305.PubMedCrossRef Dieplinger B, Lingenhel A, Baumgartner N, Poelz W, Dieplinger H, Haltmayer M, et al. Increased serum lipoprotein(a) concentrations and low molecular weight phenotypes of apolipoprotein(a) are associated with symptomatic peripheral arterial disease. Clin Chem. 2007;53:1298–305.PubMedCrossRef
5.
Zurück zum Zitat Mooser V, Berger MM, Tappy L, Cayeux C, Marcovina SM, Darioli R, et al. Major reduction in plasma Lp(a) levels during sepsis and burns. Arterioscler Thromb Vasc Biol. 2000;20:1137–42.PubMed Mooser V, Berger MM, Tappy L, Cayeux C, Marcovina SM, Darioli R, et al. Major reduction in plasma Lp(a) levels during sepsis and burns. Arterioscler Thromb Vasc Biol. 2000;20:1137–42.PubMed
6.
Zurück zum Zitat Chimienti G, Aquilino F, Rotelli MT, Russo F, Lupo L, Pepe G. Lipoprotein(a), lipids and proinflammatory cytokines in patients undergoing major abdominal surgery. Br J Surg. 2006;93:347–53.PubMedCrossRef Chimienti G, Aquilino F, Rotelli MT, Russo F, Lupo L, Pepe G. Lipoprotein(a), lipids and proinflammatory cytokines in patients undergoing major abdominal surgery. Br J Surg. 2006;93:347–53.PubMedCrossRef
7.
Zurück zum Zitat Wang J, Hu B, Kong L, Cai H, Zhang C. Native, oxidized lipoprotein(a) and lipoprotein(a) immune complex in patients with active and inactive rheumatoid arthritis: plasma concentrations and relationship to inflammation. Clin Chim Acta. 2008;390:67–71.PubMedCrossRef Wang J, Hu B, Kong L, Cai H, Zhang C. Native, oxidized lipoprotein(a) and lipoprotein(a) immune complex in patients with active and inactive rheumatoid arthritis: plasma concentrations and relationship to inflammation. Clin Chim Acta. 2008;390:67–71.PubMedCrossRef
8.
Zurück zum Zitat Poon M, Zhang X, Dunsky KG, Taubman MB, Harpel PC. Apolipoprotein (a) induces monocyte chemotactic activity in human vascular endothelial cells. Circulation. 1997;96:2514–9.PubMed Poon M, Zhang X, Dunsky KG, Taubman MB, Harpel PC. Apolipoprotein (a) induces monocyte chemotactic activity in human vascular endothelial cells. Circulation. 1997;96:2514–9.PubMed
9.
Zurück zum Zitat Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B, et al. Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J. 2006;20:559–61.PubMed Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B, et al. Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J. 2006;20:559–61.PubMed
10.
Zurück zum Zitat Netea MG, de Bont N, Demacker PN, Kullberg BJ, Jacobs LE, Verver-Jansen TJ, et al. Lipoprotein(a) inhibits lipopolysaccharide-induced tumor necrosis factor alpha production by human mononuclear cells. Infect Immun. 1998;66:2365–7.PubMed Netea MG, de Bont N, Demacker PN, Kullberg BJ, Jacobs LE, Verver-Jansen TJ, et al. Lipoprotein(a) inhibits lipopolysaccharide-induced tumor necrosis factor alpha production by human mononuclear cells. Infect Immun. 1998;66:2365–7.PubMed
11.
Zurück zum Zitat Klezovitch O, Edelstein C, Scanu AM. Stimulation of interleukin-8 production in human THP-1 macrophages by apolipoprotein(a). Evidence for a critical involvement of elements in its C-terminal domain. J Biol Chem. 2001;276:46864–9.PubMedCrossRef Klezovitch O, Edelstein C, Scanu AM. Stimulation of interleukin-8 production in human THP-1 macrophages by apolipoprotein(a). Evidence for a critical involvement of elements in its C-terminal domain. J Biol Chem. 2001;276:46864–9.PubMedCrossRef
12.
Zurück zum Zitat Edelstein C, Pfaffinger D, Hinman J, Miller E, Lipkind G, Tsimikas S, et al. Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a). J Biol Chem. 2003;278:52841–7.PubMedCrossRef Edelstein C, Pfaffinger D, Hinman J, Miller E, Lipkind G, Tsimikas S, et al. Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a). J Biol Chem. 2003;278:52841–7.PubMedCrossRef
13.
Zurück zum Zitat Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, et al. Oxidized phospholipids, Lp(a) lipoprotein and coronary artery disease. N Engl J Med. 2005;353:46–57.PubMedCrossRef Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, et al. Oxidized phospholipids, Lp(a) lipoprotein and coronary artery disease. N Engl J Med. 2005;353:46–57.PubMedCrossRef
14.
Zurück zum Zitat Hoover-Plow J, Hart E, Gong Y, Shchurin A, Schneeman T. A physiological function for apolipoprotein(a): a natural regulator of the inflammatory response. Exp Biol Med. 2009;234:28–34.CrossRef Hoover-Plow J, Hart E, Gong Y, Shchurin A, Schneeman T. A physiological function for apolipoprotein(a): a natural regulator of the inflammatory response. Exp Biol Med. 2009;234:28–34.CrossRef
15.
Zurück zum Zitat Pepe G, Chimienti G, Liuzzi GM, Lamanuzzi BL, Nardulli M, Lolli F, et al. Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood-cerebrospinal fluid barrier dysfunction. Clin Chem. 2006;52:2043–8.PubMedCrossRef Pepe G, Chimienti G, Liuzzi GM, Lamanuzzi BL, Nardulli M, Lolli F, et al. Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood-cerebrospinal fluid barrier dysfunction. Clin Chem. 2006;52:2043–8.PubMedCrossRef
16.
Zurück zum Zitat Tsurupa G, Ho-Tin-Noé B, Anglés-Cano E, Medved L. Identification and characterization of novel lysine-independent apolipoprotein(a)-binding sites in fibrin(ogen) alphaC-domains. J Biol Chem. 2003;278:37154–9.PubMedCrossRef Tsurupa G, Ho-Tin-Noé B, Anglés-Cano E, Medved L. Identification and characterization of novel lysine-independent apolipoprotein(a)-binding sites in fibrin(ogen) alphaC-domains. J Biol Chem. 2003;278:37154–9.PubMedCrossRef
17.
Zurück zum Zitat May LT, Santhanam U, Sehgal PB. On the multimeric nature of natural human interleukin-6. J Biol Chem. 1991;266:9950–5.PubMed May LT, Santhanam U, Sehgal PB. On the multimeric nature of natural human interleukin-6. J Biol Chem. 1991;266:9950–5.PubMed
18.
Zurück zum Zitat Drysdale BE, Zacharchuk CM, Shin HS. Mechanism of macrophage-mediated cytotoxicity: production of a soluble cytotoxic factor. J Immunol. 1983;131:2362–7.PubMed Drysdale BE, Zacharchuk CM, Shin HS. Mechanism of macrophage-mediated cytotoxicity: production of a soluble cytotoxic factor. J Immunol. 1983;131:2362–7.PubMed
19.
Zurück zum Zitat Schwamborn J, Lindecke A, Elvers M, Horejschi V, Kerick M, Rafigh M, et al. Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells. BMC Genomics. 2003;4:46.PubMedCrossRef Schwamborn J, Lindecke A, Elvers M, Horejschi V, Kerick M, Rafigh M, et al. Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells. BMC Genomics. 2003;4:46.PubMedCrossRef
20.
Zurück zum Zitat Palma C, Urbani F, Manzini S. Interleukin-6 production by U373 MG, a human astrocytoma cell line: different pathways involved in substance P and lipopolysaccharide activation. J Neuroimmunol. 1995;59:155–63.PubMedCrossRef Palma C, Urbani F, Manzini S. Interleukin-6 production by U373 MG, a human astrocytoma cell line: different pathways involved in substance P and lipopolysaccharide activation. J Neuroimmunol. 1995;59:155–63.PubMedCrossRef
21.
Zurück zum Zitat Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992;176:1665–71.PubMedCrossRef Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992;176:1665–71.PubMedCrossRef
22.
Zurück zum Zitat Lawn RM, Boonmark NW, Schwartz K, Lindahl GE, Wade DP, Byrne CD, et al. The recurring evolution of lipoprotein(a). Insights from cloning of hedgehog apolipoprotein(a). J Biol Chem. 1995;270:24004–9.PubMedCrossRef Lawn RM, Boonmark NW, Schwartz K, Lindahl GE, Wade DP, Byrne CD, et al. The recurring evolution of lipoprotein(a). Insights from cloning of hedgehog apolipoprotein(a). J Biol Chem. 1995;270:24004–9.PubMedCrossRef
23.
Zurück zum Zitat Han R. Plasma lipoproteins are important components of the immune system. Microbiol Immunol. 2010;54:246–53.PubMedCrossRef Han R. Plasma lipoproteins are important components of the immune system. Microbiol Immunol. 2010;54:246–53.PubMedCrossRef
24.
Zurück zum Zitat Erridge C, Kennedy S, Spickett CM, Webb DJ. Oxidised phospholipid inhibition of Toll-like receptor (TLR) signaling is restricted to TRL2 and TLR4. Roles for CD14, LPS-binding protein and MD2 as target for specificity of inhibition. J Biol Chem. 2008;283:24748–59.PubMedCrossRef Erridge C, Kennedy S, Spickett CM, Webb DJ. Oxidised phospholipid inhibition of Toll-like receptor (TLR) signaling is restricted to TRL2 and TLR4. Roles for CD14, LPS-binding protein and MD2 as target for specificity of inhibition. J Biol Chem. 2008;283:24748–59.PubMedCrossRef
25.
Zurück zum Zitat Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin MJ, et al. A novel function of lipoprotein(a) as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res. 2008;49:2230–8.PubMedCrossRef Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin MJ, et al. A novel function of lipoprotein(a) as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res. 2008;49:2230–8.PubMedCrossRef
26.
Zurück zum Zitat Bochkov VN. Inflammatory profile of oxidized phospholipids. Thromb Haemost. 2007;97:348–54.PubMed Bochkov VN. Inflammatory profile of oxidized phospholipids. Thromb Haemost. 2007;97:348–54.PubMed
27.
Zurück zum Zitat Bochkov VN, Kadl A, Huber J, Gruber F, Binder BR, Leitinger N. Protective role of phospholipids oxidation production in endotoxin-induced tissue damage. Nature. 2002;419:77–81.PubMedCrossRef Bochkov VN, Kadl A, Huber J, Gruber F, Binder BR, Leitinger N. Protective role of phospholipids oxidation production in endotoxin-induced tissue damage. Nature. 2002;419:77–81.PubMedCrossRef
28.
Zurück zum Zitat Erridge C. Oxidized phospholipid inhibition of LPS-signaling: A good side to the bad guys? Arterioscler Thromb Vasc Biol. 2009;29:337–8.PubMedCrossRef Erridge C. Oxidized phospholipid inhibition of LPS-signaling: A good side to the bad guys? Arterioscler Thromb Vasc Biol. 2009;29:337–8.PubMedCrossRef
29.
Zurück zum Zitat Pepe G, Di Perna V, Resta F, Lovecchio M, Chimienti G, Colacicco AM, et al. In search of a biological pattern for human longevity: impact of apo A-IV genetic polymorphisms on lipoproteins and the hyper-Lp(a) in centenarians. Atherosclerosis. 1998;137:407–17.PubMedCrossRef Pepe G, Di Perna V, Resta F, Lovecchio M, Chimienti G, Colacicco AM, et al. In search of a biological pattern for human longevity: impact of apo A-IV genetic polymorphisms on lipoproteins and the hyper-Lp(a) in centenarians. Atherosclerosis. 1998;137:407–17.PubMedCrossRef
30.
Zurück zum Zitat Thillet J. Doucet, C. Chapman J, Herbeth B, Cohen D, Faure-Delanef L. Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with longevity: evidence from a large population of French centenarians. Atherosclerosis. 1998;136:389–94.PubMedCrossRef Thillet J. Doucet, C. Chapman J, Herbeth B, Cohen D, Faure-Delanef L. Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with longevity: evidence from a large population of French centenarians. Atherosclerosis. 1998;136:389–94.PubMedCrossRef
31.
Zurück zum Zitat Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, et al. Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation. 2008;15:224–40.PubMedCrossRef Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, et al. Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation. 2008;15:224–40.PubMedCrossRef
Metadaten
Titel
Apolipoprotein(a) inhibits lipopolysaccharide-induced IL-6 secretion in human astrocytoma cell line by interfering with lipopolysaccharide signaling
verfasst von
Guglielmina Chimienti
Anna Mezzapesa
Grazia M. Liuzzi
Tiziana Latronico
Gabriella Pepe
Publikationsdatum
01.04.2011
Verlag
SP Birkhäuser Verlag Basel
Erschienen in
Inflammation Research / Ausgabe 4/2011
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-010-0272-7

Weitere Artikel der Ausgabe 4/2011

Inflammation Research 4/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Bei Herzinsuffizienz muss „Eisenmangel“ neu definiert werden!

16.05.2024 Herzinsuffizienz Nachrichten

Bei chronischer Herzinsuffizienz macht es einem internationalen Expertenteam zufolge wenig Sinn, die Diagnose „Eisenmangel“ am Serumferritin festzumachen. Das Team schlägt vor, sich lieber an die Transferrinsättigung zu halten.

Herzinfarkt mit 85 – trotzdem noch intensive Lipidsenkung?

16.05.2024 Hypercholesterinämie Nachrichten

Profitieren nach einem akuten Myokardinfarkt auch Betroffene über 80 Jahre noch von einer intensiven Lipidsenkung zur Sekundärprävention? Um diese Frage zu beantworten, wurden jetzt Registerdaten aus Frankreich ausgewertet.

ADHS-Medikation erhöht das kardiovaskuläre Risiko

16.05.2024 Herzinsuffizienz Nachrichten

Erwachsene, die Medikamente gegen das Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom einnehmen, laufen offenbar erhöhte Gefahr, an Herzschwäche zu erkranken oder einen Schlaganfall zu erleiden. Es scheint eine Dosis-Wirkungs-Beziehung zu bestehen.

Erstmanifestation eines Diabetes-Typ-1 bei Kindern: Ein Notfall!

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Manifestiert sich ein Typ-1-Diabetes bei Kindern, ist das ein Notfall – ebenso wie eine diabetische Ketoazidose. Die Grundsäulen der Therapie bestehen aus Rehydratation, Insulin und Kaliumgabe. Insulin ist das Medikament der Wahl zur Behandlung der Ketoazidose.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.