Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages.
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.


OBJECTIVE
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 microM 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-alpha, interleukin-1beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-kappaB.


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.
Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan.
Yoshimi
Y
Kishimoto
Mariko
M
Tani
Harumi
H
Uto-Kondo
Maki
M
Iizuka
Emi
E
Saita
Hirohito
H
Sone
Hideaki
H
Kurata
Kazuo
K
Kondo
D000975:Antioxidants / Q000494:pharmacology*; D050197:Atherosclerosis / Q000517:prevention & control; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D024341:Xanthophylls / Q000494:pharmacology*
D000975:Antioxidants; D018955:CD36 Antigens; D018836:Inflammation Mediators; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D024341:Xanthophylls; C005948:astaxanthine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020782:Matrix Metalloproteinases