Curcumin Suppresses the Induction of Indoleamine 2,3-Dioxygenase by Blocking the Janus-activated Kinase-Protein Kinase Cδ-STAT1 Signaling Pathway in Interferon-γ-stimulated Murine Dendritic Cells

被引：102

作者：

Jeong, Young-Il ^{[2
]}

Kim, Sang Woo ^{[3
]}

Jung, In Duk ^{[1
,4
]}

Lee, Jun Sik ^{[1
,4
]}

Chang, Jeong Hyun ^{[6
]}

Lee, Chang-Min ^{[1
,4
]}

Chun, Sung Hak ^{[1
,4
]}

Yoon, Man-Soo ^{[3
]}

Kim, Geun Tae ^{[7
]}

Ryu, Seok Woo ^{[8
]}

Kim, Jong-Suk ^{[9
]}

Shin, Yong Kyoo ^{[10
]}

Lee, Won Suk ^{[5
]}

Shin, Hwa Kyoung ^{[5
]}

Lee, Jae-Dong ^{[2
]}

Park, Yeong-Min ^{[1
,4
]}

机构：

[1] Pusan Natl Univ, Dept Microbiol & Immunol, Pusan 602739, South Korea

[2] Pusan Natl Univ, Coll Nat Sci, Dept Microbiol, Pusan 609735, South Korea

[3] Pusan Natl Univ, Dept Obstet & Gynecol, Pusan 602739, South Korea

[4] Pusan Natl Univ, Natl Res Lab Dendrit Cell Differentiat & Regulat, Med Res Inst, Pusan 602739, South Korea

[5] Pusan Natl Univ, Dept Pharmacol, Coll Med, Pusan 602739, South Korea

[6] Daegu Haany Univ, Coll Hlth & Therapy, Dept Clin Lab Sci, Gyeongsangbuk Do 712715, Gyeongsan, South Korea

[7] Busan Med Ctr, Dept Internal Med, Pusan 611072, South Korea

[8] Busan Med Ctr, Dept Family Med, Pusan 611072, South Korea

[9] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju 561180, South Korea

[10] Chung Ang Univ, Coll Med, Dept Pharmacol, Seoul 156756, South Korea

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 06期

关键词：

NF-KAPPA-B; TRYPTOPHAN CATABOLISM; IN-VIVO; SERINE PHOSPHORYLATION; POTENTIAL TARGETS; GENE PROMOTER; COLON-CANCER; EXPRESSION; TOLERANCE; IDO;

D O I：

10.1074/jbc.M807328200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step in the degradation of tryptophan and is strongly induced in interferon-gamma (IFN gamma)-stimulated dendritic cells (DCs). IDO has recently been established as a key enzyme in T-cell suppression-mediated immune tolerance to tumors. STAT1 phosphorylation appears to play an important role in the control of IDO expression by IFN gamma, but the precise regulatory mechanism remains obscure. Here we present a novel mechanism of IFN gamma-induced IDO expression in bone marrow-derived dendritic cells. In addition, we demonstrate that curcumin, an active component of turmeric, significantly inhibited the induction of IDO expression and activity by IFN gamma. We found that curcumin suppressed STAT1 activation by directly inhibiting Janus-activated kinase 1/2 and protein kinase C delta phosphorylation in bone marrow-derived DCs, suppressing the subsequent translocation and binding of STAT1 to the GAS element of the IRF-1 promoter. Coincident with these inhibitory effects on IFN gamma-induced IDO expression, curcumin reversed IDO-mediated suppression of T-cell responses. Our results, thus, suggest that down-regulation of IDO in DCs is an important immunomodulatory property of curcumin that may be exploited therapeutically in the control of cancers.

引用

页码：3700 / 3708

页数：9

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