Differential Role for c-Rel and C/EBPβ/δ in TLR-Mediated Induction of Proinflammatory Cytokines

被引：93

作者：

Lu, Yong-Chen ^{[1
,2
]}

Kim, Ira ^{[1
,2
]}

Lye, Elizabeth ^{[1
,2
]}

Shen, Fang ^{[4
,5
]}

Suzuki, Nobutaka ^{[6
]}

Suzuki, Shinobu ^{[7
]}

Gerondakis, Steve ^{[8
]}

Akira, Shizuo ^{[9
]}

Gaffen, Sarah L. ^{[4
,5
]}

Yeh, Wen-Chen ^{[1
,2
,3
]}

Ohashi, Pamela S. ^{[1
,2
,3
]}

机构：

[1] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[3] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[4] SUNY Buffalo, Dept Oral Biol, Sch Dent Med, Buffalo, NY 14260 USA

[5] SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14260 USA

[6] Takeda Pharmaceut Co Ltd, Tsukuba, Ibaraki, Japan

[7] Kawanishi Pharma Res Inst, Dept Mol & Cellular Biol, Kawanishi, Hyogo, Japan

[8] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[9] Osaka Univ, Japan Sci & Technol Corp, Res Inst Microbial Dis & Exploratory Res Adv Tech, Dept Host Def, Osaka, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 11期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

NF-KAPPA-B; CCAAT/ENHANCER BINDING-PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; LEUCINE-ZIPPER PROTEINS; BETA-DEFICIENT MICE; TOLL-LIKE RECEPTORS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSES;

D O I：

10.4049/jimmunol.0802971

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-associated kinase 4 that is essential for proinflammatory cytokine induction. Although NF-kappa B has been shown to be one of the key transcriptional regulators of these cytokines, evidence suggests that other factors may also be important. In this study, we showed that MyD88-deficient macrophages have defective c-Rel activation, which has been linked to IL-12p40 induction, but not IL-6 or TNF-alpha. We also investigated other transcription factors and showed that C/EBP beta and C/EBP delta expression was limited in MyD88- or IL-1R-associated kinase 4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBP beta and C/EBP delta resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBP beta/delta as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines. The Journal of Immunology, 2009, 182: 7212-7221.

引用

页码：7212 / 7221

页数：10

共 85 条

[1] Pathogen recognition and innate immunity [J].

Akira, S ;

Uematsu, S ;

Takeuchi, O .

CELL, 2006, 124 (04) :783-801

[2] A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY [J].

AKIRA, S ;

ISSHIKI, H ;

SUGITA, T ;

TANABE, O ;

KINOSHITA, S ;

NISHIO, Y ;

NAKAJIMA, T ;

HIRANO, T ;

KISHIMOTO, T .

EMBO JOURNAL, 1990, 9 (06) :1897-1906

[3] Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP [J].

Andreakos, E ;

Sacre, SM ;

Smith, C ;

Lundberg, A ;

Kiriakidis, S ;

Stonehouse, T ;

Monaco, C ;

Feldmann, M ;

Foxwell, BM .

BLOOD, 2004, 103 (06) :2229-2237

[4] Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large [J].

Beutler, Bruce ;

Jiang, Zhengfan ;

Georgel, Philippe ;

Crozat, Karine ;

Croker, Ben ;

Rutschmann, Sophie ;

Du, Xin ;

Hoebe, Kasper .

ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :353-389

[5] Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes [J].

Boffa, DJ ;

Feng, B ;

Sharma, V ;

Dematteo, R ;

Miller, G ;

Suthanthiran, M ;

Nunez, R ;

Liou, HC .

CELLULAR IMMUNOLOGY, 2003, 222 (02) :105-115

[6] The two NF-κB activation pathways and their role in innate and adaptive immunity [J].

Bonizzi, G ;

Karin, M .

TRENDS IN IMMUNOLOGY, 2004, 25 (06) :280-288

[7] C/EBPβ regulation in lipopolysaccharide-stimulated macrophages [J].

Bradley, MN ;

Zhou, LA ;

Smale, ST .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) :4841-4858

[8] C/EBP-RELATED PROTEIN-2 CONFERS LIPOPOLYSACCHARIDE-INDUCIBLE EXPRESSION OF INTERLEUKIN-6 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 TO A LYMPHOBLASTIC CELL-LINE [J].

BRETZ, JD ;

WILLIAMS, SC ;

BAER, M ;

JOHNSON, PF ;

SCHWARTZ, RC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (15) :7306-7310

[9] Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis [J].

Campbell, IK ;

Gerondakis, S ;

O'Donnell, K ;

Wicks, IP .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (12) :1799-1806

[10] REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].

CAO, ZD ;

UMEK, RM ;

MCKNIGHT, SL .

GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552

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