Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages

被引:71
作者
Park, Sun Young [2 ,3 ]
Park, Da Jung [1 ]
Kim, Young Hun [2 ]
Kim, YoungHee [1 ,3 ]
Kim, Sun Gun
Shon, Kwang Jae [4 ]
Choi, Young-Whan [1 ]
Lee, Sang-Joon [5 ]
机构
[1] Pusan Natl Univ, Dept Hort Biosci, Miryang 627706, South Korea
[2] Pusan Natl Univ, BioIT Fus Technol Res Inst, Pusan 609735, South Korea
[3] Pusan Natl Univ, Dept Mol Biol, Pusan 609735, South Korea
[4] Pusan Natl Univ, Ctr Res Facil, Pusan 609735, South Korea
[5] Pusan Natl Univ, Dept Microbiol, Pusan 609735, South Korea
关键词
Schisandrin; Porphyromonas gingivalis LPS; Pro-inflammatory cytokine; NF-kappa B; Heme oxygenase-1; Nrf-2; INFLAMMATORY CYTOKINE RELEASE; SCHIZANDRA-CHINENSIS BAILL; MOLECULAR-MECHANISMS; ACTIVATION; EXPRESSION; LIPOPOLYSACCHARIDE; CONSTITUENTS; SURFACTIN; CURCUMIN; LIGNANS;
D O I
10.1016/j.imlet.2011.05.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lipopolysaccharide (LPS) of Porphyromonas gingivalis is thought to induce periodontitis. In this study, we isolated Schisandrin from the dried fruits of Schisandra chinensis and examined the anti-inflammatory effect of Schisandrin in macrophages stimulated with LPS from P. gingivalis. First, Schisandrin inhibited LPS-induced pro-inflammatory cytokines, including TNF-alpha, IL-1 beta, and IL-6. And Schisandrin suppressed the nuclear translocation and activity of NF-kappa B and phosphorylation of I kappa B alpha in LPS-stimulated RAW 264.7 cells. Next, the presence of a selective inhibitor of HO-1 (SnPP) and a siRNA specific for HO-1 inhibited Schisandrin-mediated anti-inflammatory activity. Furthermore, Schisandrin induced HO-1 expression of RAW 264.7 cells through Nrf-2, PI3K/Akt, and ERK activation. Therefore, these results suggest that the anti-inflammatory effects of Schisandrin on P. gingivalis LPS-stimulated RAW 264.7 cells may be due to a reduction of NF-kappa B activity and induction of the expression of HO-1, leading to INF-alpha, IL-10, and IL-6 down-regulation. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:93 / 101
页数:9
相关论文
共 31 条
[1]   Heme oxygenase-1 mediates the anti-inflammatory actions of 2′-hydroxychalcone in RAW 264.7 murine macrophages [J].
Abuarqoub, H ;
Foresti, R ;
Green, CJ ;
Motterlini, R .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2006, 290 (04) :C1092-C1099
[2]   Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells [J].
Chen, CY ;
Jang, JH ;
Li, MH ;
Surh, YJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 331 (04) :993-1000
[3]   Inhibition of endothelial cell adhesion by the new anti-inflammatory agent α-iso-cubebene [J].
Choi, Young-Whan ;
Kim, Hyo Jin ;
Park, Sung-Sam ;
Chung, Jae-Heun ;
Lee, Hee-Woo ;
Oh, Sae-Ock ;
Kim, Bong-Seon ;
Kim, Jae-Bong ;
Chung, Hae-Young ;
Yu, Byung-Pal ;
Kim, Chi-Dae ;
Yoon, Sik .
VASCULAR PHARMACOLOGY, 2009, 51 (04) :215-224
[4]   Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis:: Structure-antioxidant activity relationships of dibenzocyclooctadiene lignans [J].
Choi, YW ;
Takamatsu, S ;
Khan, SI ;
Srinivas, PV ;
Ferreira, D ;
Zhao, JP ;
Khan, IA .
JOURNAL OF NATURAL PRODUCTS, 2006, 69 (03) :356-359
[5]   4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway [J].
Furukawa, Yoshiko ;
Urano, Tomomi ;
Minamimura, Misato ;
Nakajima, Mitsunari ;
Okuyama, Satoshi ;
Furukawa, Shoei .
BIOMEDICAL RESEARCH-TOKYO, 2010, 31 (01) :45-52
[6]   Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease [J].
Gemmell, E ;
Marshall, RI ;
Seymour, GJ .
PERIODONTOLOGY 2000, 1997, 14 :112-143
[7]   Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill [J].
Guo, Lian Yu ;
Hung, Tran Manh ;
Bae, Ki Hwan ;
Shin, Eun Myoung ;
Zhou, Hong Yu ;
Hong, Yoo Na ;
Kang, Sam Sik ;
Kim, Hyun Pyo ;
Kim, Yeong Shik .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2008, 591 (1-3) :293-299
[8]   Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis [J].
Han, SJ ;
Jeong, SY ;
Nam, YJ ;
Yang, KH ;
Lim, HS ;
Chung, J .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 2005, 12 (11) :1285-1291
[9]  
IKEYA Y, 1980, CHEM PHARM BULL, V28, P2414
[10]  
IKEYA Y, 1979, CHEM PHARM BULL, V27, P1383