Skip to main content
Erschienen in: European Journal of Nutrition 2/2010

01.03.2010 | Original Contribution

Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages

verfasst von: Yoshimi Kishimoto, Mariko Tani, Harumi Uto-Kondo, Maki Iizuka, Emi Saita, Hirohito Sone, Hideaki Kurata, Kazuo Kondo

Erschienen in: European Journal of Nutrition | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages.

Aim of the study

In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages.

Methods

THP-1 macrophages were incubated with 5–10 μM astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry.

Results

We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-κB.

Conclusions

These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.
Literatur
1.
Zurück zum Zitat Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87:13–20CrossRef Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87:13–20CrossRef
2.
Zurück zum Zitat Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T (2003) Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 253:269–285CrossRef Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T (2003) Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 253:269–285CrossRef
3.
Zurück zum Zitat Chase AJ, Bond M, Crook MF, Newby AC (2002) Role of nuclear factor-kappa B activation in metalloproteinase-1, -3, and -9 secretion by human macrophages in vitro and rabbit foam cells produced in vivo. Arterioscler Thromb Vasc Biol 22:765–771CrossRef Chase AJ, Bond M, Crook MF, Newby AC (2002) Role of nuclear factor-kappa B activation in metalloproteinase-1, -3, and -9 secretion by human macrophages in vitro and rabbit foam cells produced in vivo. Arterioscler Thromb Vasc Biol 22:765–771CrossRef
4.
Zurück zum Zitat Chen F, Eriksson P, Hansson GK, Herzfeld I, Klein M, Hansson LO, Valen G (2005) Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque. Int J Mol Med 15:57–65 Chen F, Eriksson P, Hansson GK, Herzfeld I, Klein M, Hansson LO, Valen G (2005) Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque. Int J Mol Med 15:57–65
5.
Zurück zum Zitat Chew BP, Park JS, Wong MW, Wong TS (1999) A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res 19:1849–1853 Chew BP, Park JS, Wong MW, Wong TS (1999) A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res 19:1849–1853
6.
Zurück zum Zitat De Waart FG, Schouten EG, Stalenhoef AF, Kok FJ (2001) Serum carotenoids, alpha-tocopherol and mortality risk in a prospective study among Dutch elderly. Int J Epidemiol 30:136–143CrossRef De Waart FG, Schouten EG, Stalenhoef AF, Kok FJ (2001) Serum carotenoids, alpha-tocopherol and mortality risk in a prospective study among Dutch elderly. Int J Epidemiol 30:136–143CrossRef
7.
Zurück zum Zitat Devaraj S, Hugou I, Jialal I (2001) Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages. J Lipid Res 42:521–527 Devaraj S, Hugou I, Jialal I (2001) Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages. J Lipid Res 42:521–527
8.
Zurück zum Zitat Eguchi A, Murakami A, Ohigashi H (2006) Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. FEBS Lett 580:3321–3328CrossRef Eguchi A, Murakami A, Ohigashi H (2006) Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. FEBS Lett 580:3321–3328CrossRef
9.
Zurück zum Zitat Evans RW, Shaten BJ, Day BW, Kuller LH (1998) Prospective association between lipid soluble antioxidants and coronary heart disease in men. The multiple risk factor intervention trial. Am J Epidemiol 147:180–186 Evans RW, Shaten BJ, Day BW, Kuller LH (1998) Prospective association between lipid soluble antioxidants and coronary heart disease in men. The multiple risk factor intervention trial. Am J Epidemiol 147:180–186
10.
Zurück zum Zitat Fukuhara-Takaki K, Sakai M, Sakamoto Y, Takeya M, Horiuchi S (2005) Expression of class A scavenger receptor is enhanced by high glucose in vitro and under diabetic conditions in vivo: one mechanism for an increased rate of atherosclerosis in diabetes. J Biol Chem 280:3355–3364CrossRef Fukuhara-Takaki K, Sakai M, Sakamoto Y, Takeya M, Horiuchi S (2005) Expression of class A scavenger receptor is enhanced by high glucose in vitro and under diabetic conditions in vivo: one mechanism for an increased rate of atherosclerosis in diabetes. J Biol Chem 280:3355–3364CrossRef
11.
Zurück zum Zitat Fukuzawa K, Inokami Y, Tokumura A, Terao J, Suzuki A (1998) Rate constants for quenching singlet oxygen and activities for inhibiting lipid peroxidation of carotenoids and alpha-tocopherol in liposomes. Lipids 33:751–756CrossRef Fukuzawa K, Inokami Y, Tokumura A, Terao J, Suzuki A (1998) Rate constants for quenching singlet oxygen and activities for inhibiting lipid peroxidation of carotenoids and alpha-tocopherol in liposomes. Lipids 33:751–756CrossRef
12.
Zurück zum Zitat Galis ZS, Asanuma K, Godin D, Meng X (1998) N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation 97:2445–2453 Galis ZS, Asanuma K, Godin D, Meng X (1998) N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation 97:2445–2453
13.
Zurück zum Zitat Giansante C, Fiotti N, Di Chiara A, Altamura N, Wasserman S, Fioretti P, Guarnieri G (2007) In-hospital outcome of patients with acute coronary syndrome: relationship with inflammation and remodeling markers. J Cardiovasc Med (Hagerstown) 8:602–607 Giansante C, Fiotti N, Di Chiara A, Altamura N, Wasserman S, Fioretti P, Guarnieri G (2007) In-hospital outcome of patients with acute coronary syndrome: relationship with inflammation and remodeling markers. J Cardiovasc Med (Hagerstown) 8:602–607
14.
Zurück zum Zitat Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H (2001) Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 1512:251–258CrossRef Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H (2001) Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 1512:251–258CrossRef
15.
Zurück zum Zitat Gross GJ, Lockwood SF (2005) Acute and chronic administration of disodium disuccinate astaxanthin (Cardax) produces marked cardioprotection in dog hearts. Mol Cell Biochem 272:221–227CrossRef Gross GJ, Lockwood SF (2005) Acute and chronic administration of disodium disuccinate astaxanthin (Cardax) produces marked cardioprotection in dog hearts. Mol Cell Biochem 272:221–227CrossRef
16.
Zurück zum Zitat Gross GJ, Lockwood SF (2004) Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax). Life Sci 75:215–224CrossRef Gross GJ, Lockwood SF (2004) Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax). Life Sci 75:215–224CrossRef
17.
Zurück zum Zitat Inokubo Y, Hanada H, Ishizaka H, Fukushi T, Kamada T, Okumura K (2001) Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome. Am Heart J 141:211–217CrossRef Inokubo Y, Hanada H, Ishizaka H, Fukushi T, Kamada T, Okumura K (2001) Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome. Am Heart J 141:211–217CrossRef
18.
Zurück zum Zitat Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M, Itakura H, Yamamoto S, Kondo K (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb 7:216–222 Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M, Itakura H, Yamamoto S, Kondo K (2000) Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb 7:216–222
19.
Zurück zum Zitat Jacobsson LS, Yuan XM, Zieden B, Olsson AG (2004) Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits. Atherosclerosis 173:231–237 Jacobsson LS, Yuan XM, Zieden B, Olsson AG (2004) Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits. Atherosclerosis 173:231–237
20.
Zurück zum Zitat Jung WJ, Sung MK (2004) Effects of major dietary antioxidants on inflammatory markers of RAW 264.7 macrophages. Biofactors (Oxford) 21:113–117CrossRef Jung WJ, Sung MK (2004) Effects of major dietary antioxidants on inflammatory markers of RAW 264.7 macrophages. Biofactors (Oxford) 21:113–117CrossRef
21.
Zurück zum Zitat Jyonouchi H, Sun S, Iijima K, Gross MD (2000) Antitumor activity of astaxanthin and its mode of action. Nutr Cancer 36:59–65CrossRef Jyonouchi H, Sun S, Iijima K, Gross MD (2000) Antitumor activity of astaxanthin and its mode of action. Nutr Cancer 36:59–65CrossRef
22.
Zurück zum Zitat Kawai Y, Nishikawa T, Shiba Y, Saito S, Murota K, Shibata N, Kobayashi M, Kanayama M, Uchida K, Terao J (2008) Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. J Biol Chem 283:9424–9434CrossRef Kawai Y, Nishikawa T, Shiba Y, Saito S, Murota K, Shibata N, Kobayashi M, Kanayama M, Uchida K, Terao J (2008) Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. J Biol Chem 283:9424–9434CrossRef
23.
Zurück zum Zitat Kim GY, Kim JH, Ahn SC, Lee HJ, Moon DO, Lee CM, Park YM (2004) Lycopene suppresses the lipopolysaccharide-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB. Immunology 113:203–211CrossRef Kim GY, Kim JH, Ahn SC, Lee HJ, Moon DO, Lee CM, Park YM (2004) Lycopene suppresses the lipopolysaccharide-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB. Immunology 113:203–211CrossRef
24.
Zurück zum Zitat Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW (2002) Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem 277:49982–49988CrossRef Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW (2002) Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem 277:49982–49988CrossRef
25.
Zurück zum Zitat Lauver DA, Driscoll EM, Lucchesi BR (2008) Disodium disuccinate astaxanthin prevents carotid artery rethrombosis and ex vivo platelet activation. Pharmacology 82:67–73CrossRef Lauver DA, Driscoll EM, Lucchesi BR (2008) Disodium disuccinate astaxanthin prevents carotid artery rethrombosis and ex vivo platelet activation. Pharmacology 82:67–73CrossRef
26.
Zurück zum Zitat Lendon CL, Davies MJ, Born GV, Richardson PD (1991) Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis 87:87–90CrossRef Lendon CL, Davies MJ, Born GV, Richardson PD (1991) Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis 87:87–90CrossRef
27.
Zurück zum Zitat Liao YF, Hung HC, Hsu PC, Kao MC, Hour TC, Tsay GJ, Liu GY (2008) Ornithine decarboxylase interferes with macrophage-like differentiation and matrix metalloproteinase-9 expression by tumor necrosis factor alpha via NF-kappaB. Leuk Res 32:1124–1140CrossRef Liao YF, Hung HC, Hsu PC, Kao MC, Hour TC, Tsay GJ, Liu GY (2008) Ornithine decarboxylase interferes with macrophage-like differentiation and matrix metalloproteinase-9 expression by tumor necrosis factor alpha via NF-kappaB. Leuk Res 32:1124–1140CrossRef
28.
Zurück zum Zitat Mamputu JC, Li L, Renier G (2006) Gliclazide inhibits differentiation-associated biologic events in human monocyte-derived macrophages. Metab Clin Exp 55:778–785 Mamputu JC, Li L, Renier G (2006) Gliclazide inhibits differentiation-associated biologic events in human monocyte-derived macrophages. Metab Clin Exp 55:778–785
29.
Zurück zum Zitat Miller YI, Chang MK, Binder CJ, Shaw PX, Witztum JL (2003) Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol 14:437–445CrossRef Miller YI, Chang MK, Binder CJ, Shaw PX, Witztum JL (2003) Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol 14:437–445CrossRef
30.
Zurück zum Zitat Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Bohm BO, Winkelmann BR, Marz W, Fuchs D (2009) Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 202:543–549CrossRef Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Bohm BO, Winkelmann BR, Marz W, Fuchs D (2009) Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 202:543–549CrossRef
31.
Zurück zum Zitat Naguib YM (2000) Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem 48:1150–1154CrossRef Naguib YM (2000) Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem 48:1150–1154CrossRef
32.
Zurück zum Zitat Newby AC (2008) Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol 28:2108–2114CrossRef Newby AC (2008) Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol 28:2108–2114CrossRef
33.
Zurück zum Zitat Ozer NK, Negis Y, Aytan N, Villacorta L, Ricciarelli R, Zingg JM, Azzi A (2006) Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits. Atherosclerosis 184:15–20CrossRef Ozer NK, Negis Y, Aytan N, Villacorta L, Ricciarelli R, Zingg JM, Azzi A (2006) Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits. Atherosclerosis 184:15–20CrossRef
34.
Zurück zum Zitat Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Pioli C, Wolf FI, Calviello G (2003) Beta-carotene regulates NF-kappaB DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. J Nutr 133:381–388 Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Pioli C, Wolf FI, Calviello G (2003) Beta-carotene regulates NF-kappaB DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. J Nutr 133:381–388
35.
Zurück zum Zitat Ross R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138:S419–S420CrossRef Ross R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138:S419–S420CrossRef
36.
Zurück zum Zitat Singh U, Devaraj S, Jialal I (2005) Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 25:151–174CrossRef Singh U, Devaraj S, Jialal I (2005) Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 25:151–174CrossRef
37.
Zurück zum Zitat Vaday GG, Franitza S, Schor H, Hecht I, Brill A, Cahalon L, Hershkoviz R, Lider O (2001) Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix. J Leukoc Biol 69:885–892 Vaday GG, Franitza S, Schor H, Hecht I, Brill A, Cahalon L, Hershkoviz R, Lider O (2001) Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix. J Leukoc Biol 69:885–892
38.
Zurück zum Zitat Walrand S, Farges MC, Dehaese O, Cardinault N, Minet-Quinard R, Grolier P, Bouteloup-Demange C, Ribalta J, Winklhofer-Roob BM, Rock E, Vasson MP (2005) In vivo and in vitro evidences that carotenoids could modulate the neutrophil respiratory burst during dietary manipulation. Eur J Nutr 44:114–120CrossRef Walrand S, Farges MC, Dehaese O, Cardinault N, Minet-Quinard R, Grolier P, Bouteloup-Demange C, Ribalta J, Winklhofer-Roob BM, Rock E, Vasson MP (2005) In vivo and in vitro evidences that carotenoids could modulate the neutrophil respiratory burst during dietary manipulation. Eur J Nutr 44:114–120CrossRef
39.
Zurück zum Zitat Watanabe N, Ikeda U (2004) Matrix metalloproteinases and atherosclerosis. Curr Atheroscler Rep 6:112–120CrossRef Watanabe N, Ikeda U (2004) Matrix metalloproteinases and atherosclerosis. Curr Atheroscler Rep 6:112–120CrossRef
40.
Zurück zum Zitat Woo JH, Park JW, Lee SH, Kim YH, Lee IK, Gabrielson E, Lee SH, Lee HJ, Kho YH, Kwon TK (2003) Dykellic acid inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting nuclear factor kappa B transcriptional activity. Cancer Res 63:3430–3434 Woo JH, Park JW, Lee SH, Kim YH, Lee IK, Gabrielson E, Lee SH, Lee HJ, Kho YH, Kwon TK (2003) Dykellic acid inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting nuclear factor kappa B transcriptional activity. Cancer Res 63:3430–3434
41.
Zurück zum Zitat Zeng B, Prasan A, Fung KC, Solanki V, Bruce D, Freedman SB, Brieger D (2005) Elevated circulating levels of matrix metalloproteinase-9 and -2 in patients with symptomatic coronary artery disease. Intern Med J 35:331–335CrossRef Zeng B, Prasan A, Fung KC, Solanki V, Bruce D, Freedman SB, Brieger D (2005) Elevated circulating levels of matrix metalloproteinase-9 and -2 in patients with symptomatic coronary artery disease. Intern Med J 35:331–335CrossRef
42.
Zurück zum Zitat Zhou M, Zhang Y, Ardans JA, Wahl LM (2003) Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8. J Biol Chem 278:45406–45413CrossRef Zhou M, Zhang Y, Ardans JA, Wahl LM (2003) Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8. J Biol Chem 278:45406–45413CrossRef
Metadaten
Titel
Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages
verfasst von
Yoshimi Kishimoto
Mariko Tani
Harumi Uto-Kondo
Maki Iizuka
Emi Saita
Hirohito Sone
Hideaki Kurata
Kazuo Kondo
Publikationsdatum
01.03.2010
Verlag
Springer-Verlag
Erschienen in
European Journal of Nutrition / Ausgabe 2/2010
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-009-0056-4

Weitere Artikel der Ausgabe 2/2010

European Journal of Nutrition 2/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

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