Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity

被引：211

作者：

Aliberti, J ^{[1
]}

Hieny, S

Sousa, CRE

Serhan, CN

Sher, A

机构：

[1] Natl Inst Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD 20892 USA

[2] Imperial Canc Res Fund, Immunobiol Lab, London, England

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA USA

[4] Imperial Canc Res Fund, Immunobiol Lab, London, England

[5] Natl Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD USA

来源：

NATURE IMMUNOLOGY | 2002年 / 3卷 / 01期

关键词：

D O I：

10.1038/ni745

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A(4) (LXA(4)) accompanied the In vivo suppression of interleukin 12 (IL-12) responsiveness of murine splenic dendritic cells (DCs) after microbial stimulation with an extract of Toxoplasma gondii. This paralysis of DC function could not be triggered in mice that were deficient in a key lipoxygenase involved in LXA4 biosynthesis. In addition, DCs pre-treated with LXA4 became refractory to microbial stimulation for IL-12 production In vitro and mice injected with a stable LXA(4) analog showed reduced splenic DC mobilization and IL-12 responses in vivo. Together, these findings indicate that the induction of lipoxins in response to microbial stimulation can provide a potent mechanism for regulating DC function during the innate response to pathogens.

引用

页码：76 / 82

页数：7

共 33 条

[1] CCR5 provides a signal for microbial induced production of IL-12 by CD8α+ dendritic cells [J].

Aliberti, J ;

Sousa, CRE ;

Schito, M ;

Hieny, S ;

Wells, T ;

Huffnagle, GB ;

Sher, A .

NATURE IMMUNOLOGY, 2000, 1 (01) :83-87

[2] Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes [J].

Braun, MC ;

Wang, JM ;

Lahey, E ;

Rabin, RL ;

Kelsall, BL .

BLOOD, 2001, 97 (11) :3531-3536

[3] Regulation of interleukin-12 production by G-protein-coupled receptors [J].

Braun, MC ;

Kelsall, BL .

MICROBES AND INFECTION, 2001, 3 (02) :99-107

[4] The change in leukotrienes and lipoxins in activated mouse peritoneal macrophages [J].

Calorini, L ;

Mannini, A ;

Bianchini, F ;

Mugnai, G ;

Ruggieri, S .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1484 (2-3) :87-92

[5] Activation of lipoxin A4 receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation [J].

Chiang, N ;

Fierro, IM ;

Gronert, K ;

Serhan, CN .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (07) :1197-1207

[6] Oxidoreductases in lipoxin A4 metabolic inactivation -: A novel role for 15-oxoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in inflammation [J].

Clish, CB ;

Levy, BD ;

Chiang, N ;

Tai, HH ;

Serhan, CN .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25372-25380

[7] A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R [J].

Deng, XY ;

Ueda, H ;

Su, SB ;

Gong, WH ;

Dunlop, NM ;

Gao, JL ;

Murphy, PM ;

Wang, JM .

BLOOD, 1999, 94 (04) :1165-1173

[8]

FUNK CD, 1995, ADV PROSTAG THROMB L, V23, P145

[9]

Gazzinelli RT, 1996, J IMMUNOL, V157, P798

[10] Biochemical characterization and protein kinase C dependency of monokine-inducing activities of Toxoplasma gondii [J].

Grunvald, E ;

Chiaramonte, M ;

Hieny, S ;

Wysocka, M ;

Trinchieri, G ;

Vogel, SN ;

Gazzinelli, RT ;

Sher, A .

INFECTION AND IMMUNITY, 1996, 64 (06) :2010-2018

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