Human endothelial cells express NOD2/CRD15 and increase IL-6 secretion in response to muramyl dipeptide

被引:54
作者
Davey, MP
Martin, TM
Planck, SR
Lee, J
Zamora, D
Rosenbaum, JT
机构
[1] Dept Vet Affairs Med Ctr, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA
[3] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA
[4] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA
[5] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA
关键词
NOD2; gene; endothelial cells; gene expression; muramyl dipeptide; interleukin-6; Blau syndrome;
D O I
10.1016/j.mvr.2005.11.010
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Mutations in the human NOD2/CARD15 gene cause Blau syndrome, an auto inflammatory disorder involving the joints, skin and eyes. Insights into the mechanism of this association may be gained by a further understanding of where NOD2 is expressed. The objective of this study was to analyze ocular endothelial cells for NOD2 expression. Human ocular tissue was analyzed by immunohistology using anti-NOD2 antisera. RNA isolated from iris, choroid and endothelial cell lines was analyzed by reverse transcription-PCR and real-time quantitative PCR. Gene regulation was studied by treating endothelial cells with TNF-alpha and IFN-gamma. Functional responses were assessed by measuring IL-6 release from endothelial cells treated with muramyl dipeptide (MDP), synthetic lipopeptide (Pam3CSK4) and lipopolysaccharide (LPS). Immunohistological analysis revealed staining of endothelial cells in the uveal tract. NOD2 expression was detected in primary ocular endothelial cell cultures, and levels increased in response to inflammatory cytokines. Endothelial cells from choroid demonstrated enhanced release of IL-6 in response to MDP, and synergy was observed following treatment with MDP and either Pam3CSK4 or LPS. The observations that endothelial cells express NOD2, upregulate NOD2 in response to stimuli known to promote NOD2 expression and show synergistic cytokine responses to MDP and TLR ligands previously shown to be mediated by NOD2 are informative since they may be relevant to pathogenic mechanisms leading to the spectrum of inflammation seen in Blau syndrome. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:103 / 107
页数:5
相关论文
共 29 条
[1]   FAMILIAL GRANULOMATOUS ARTHRITIS, IRITIS, AND RASH [J].
BLAU, EB .
JOURNAL OF PEDIATRICS, 1985, 107 (05) :689-693
[2]   Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases [J].
Chamaillard, M ;
Philpott, D ;
Girardin, SE ;
Zouali, H ;
Lesage, S ;
Chareyre, F ;
Bui, TH ;
Giovannini, M ;
Zaehringer, U ;
Penard-Lacronique, V ;
Sansonetti, PJ ;
Hugot, JP ;
Thomas, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (06) :3455-3460
[3]   NOD2 and Crohn's disease: Loss or gain of function? [J].
Eckmann, L ;
Karin, M .
IMMUNITY, 2005, 22 (06) :661-667
[4]   Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection [J].
Girardin, SE ;
Boneca, IG ;
Viala, J ;
Chamaillard, M ;
Labigne, A ;
Thomas, G ;
Philpott, DJ ;
Sansonetti, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :8869-8872
[5]   Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-κB activation [J].
Gutierrez, O ;
Pipaon, C ;
Inohara, N ;
Fontalba, A ;
Ogura, Y ;
Prosper, F ;
Nuñez, G ;
Fernandez-Luna, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) :41701-41705
[6]   CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells [J].
Hisamatsu, T ;
Suzuki, M ;
Reinecker, HC ;
Nadeau, WJ ;
McCormick, BA ;
Podolsky, DK .
GASTROENTEROLOGY, 2003, 124 (04) :993-1000
[7]   Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease [J].
Hugot, JP ;
Chamaillard, M ;
Zouali, H ;
Lesage, S ;
Cézard, JP ;
Belaiche, J ;
Almer, S ;
Tysk, C ;
O'Morain, CA ;
Gassull, M ;
Binder, V ;
Finkel, Y ;
Cortot, A ;
Modigliani, R ;
Laurent-Puig, P ;
Gower-Rousseau, C ;
Macry, J ;
Colombel, JF ;
Sahbatou, M ;
Thomas, G .
NATURE, 2001, 411 (6837) :599-603
[8]   Host recognition of bacterial muramyl dipeptide mediated through NOD2 [J].
Inohara, N ;
Ogura, Y ;
Fontalba, A ;
Gutierrez, O ;
Pons, F ;
Crespo, J ;
Fukase, K ;
Inamura, S ;
Kusumoto, S ;
Hashimoto, M ;
Foster, SJ ;
Moran, AP ;
Fernandez-Luna, JL ;
Nuñez, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (08) :5509-5512
[9]   FAMILIAL GRANULOMATOUS SYNOVITIS, UVEITIS, AND CRANIAL NEUROPATHIES [J].
JABS, DA ;
HOUK, JL ;
BIAS, WB ;
ARNETT, FC .
AMERICAN JOURNAL OF MEDICINE, 1985, 78 (05) :801-804
[10]   Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-κB activation:: common genetic etiology with Blau syndrome [J].
Kanazawa, N ;
Okafuji, I ;
Kambe, N ;
Nishikomori, R ;
Nakata-Hizume, M ;
Nagai, S ;
Fuji, A ;
Yuasa, T ;
Manki, A ;
Sakurai, Y ;
Nakajima, M ;
Kobayashi, H ;
Fujiwara, L ;
Tsutsumi, H ;
Utani, A ;
Nishigori, C ;
Heike, T ;
Nakahata, T ;
Miyachi, Y .
BLOOD, 2005, 105 (03) :1195-1197