共 28 条
Mucosal Gene Expression of Cell Adhesion Molecules, Chemokines, and Chemokine Receptors in Patients With Inflammatory Bowel Disease Before and After Infliximab Treatment
被引:120
作者:

Arijs, Ingrid
论文数: 0 引用数: 0
h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium
Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

De Hertogh, Gert
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Hosp Gasthuisberg, Dept Morphol & Mol Pathol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Machiels, Kathleen
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Van Steen, Kristel
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Liege, Inst Montefiore, Dept Elect Engn & Comp Sci, B-4000 Liege, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Lemaire, Katleen
论文数: 0 引用数: 0
h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Schraenen, Anica
论文数: 0 引用数: 0
h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Van Lommel, Leentje
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h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Quintens, Roel
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h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Van Assche, Gert
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Vermeire, Severine
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h-index: 0
机构:
Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Schuit, Frans
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h-index: 0
机构:
Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium

Rutgeerts, Paul
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium
Univ Hosp Gasthuisberg, Leuven Food Sci & Nutr Res Ctr LFoRCe, B-3000 Louvain, Belgium Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium
机构:
[1] Katholieke Univ Leuven, Gene Express Unit, Dept Mol Cell Biol, B-3000 Louvain, Belgium
[2] Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium
[3] Univ Hosp Gasthuisberg, Dept Morphol & Mol Pathol, B-3000 Louvain, Belgium
[4] Univ Liege, Inst Montefiore, Dept Elect Engn & Comp Sci, B-4000 Liege, Belgium
[5] Univ Hosp Gasthuisberg, Leuven Food Sci & Nutr Res Ctr LFoRCe, B-3000 Louvain, Belgium
关键词:
HUMANIZED ANTIBODY;
ULCERATIVE-COLITIS;
EPITHELIAL-CELLS;
CROHNS-DISEASE;
COLON;
D O I:
10.1038/ajg.2011.27
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
OBJECTIVES: Inflammatory bowel disease (IBD) is characterized by a continuous influx of leukocytes into the gut wall. This migration is regulated by cell adhesion molecules (CAMs), and selective antimigration therapies have been developed. This study investigated the effect of infliximab therapy on the mucosal gene expression of CAMs in IBD. METHODS: Mucosal gene expression of 69 leukocyte/endothelial CAMs and E-cadherin was investigated in 61 IBD patients before and after first infliximab infusion and in 12 normal controls, using Affymetrix gene expression microarrays. Quantitative reverse transcriptase-PCR (qRT-PCR), immunohistochemistry, and western blotting were used to confirm the microarray data. RESULTS: When compared with control colons, the colonic mucosal gene expression of most leukocyte/endothelial adhesion molecules was upregulated and E-cadherin gene expression was downregulated in active colonic IBD (IBDc) before therapy, with no significant colonic gene expression differences between ulcerative colitis and colonic Crohn's disease. Infliximab therapy restored the upregulations of leukocyte CAMs in IBDc responders to infliximab that paralleled the disappearance of the inflammatory cells from the colonic lamina propria. Also, the colonic gene expression of endothelial CAMs and of most chemokines/chemokine receptors returned to normal after therapy in IBDc responders, and only CCL20 and CXCL1-2 expression remained increased after therapy in IBDc responders vs. control colons. When compared with control ileums, the ileal gene expression of MADCAM1, THY1, PECAM1, CCL28, CXCL1, -2, -5, -6, and -11, and IL8 was increased and CD58 expression was decreased in active ileal Crohn's disease (CDi) before therapy, and none of the genes remained dysregulated after therapy in CDi responders vs. control ileums. This microarray study identified a number of interesting targets for antiadhesion therapy including PECAM1, IL8, and CCL20, besides the currently studied alpha 4 beta 7 integrin-MADCAM1 axis. CONCLUSIONS: Our data demonstrate that many leukocyte/endothelial CAMs and chemokines/chemokine receptors are upregulated in inflamed IBD mucosa. Controlling the inflammation with infliximab restores most of these dysregulations in IBD. These results show that at least part of the mechanism of antitumor necrosis factor-alpha therapy goes through downregulation of certain adhesion molecules.
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页码:748 / 761
页数:14
相关论文
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Ma, K.
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机构: Katholieke Univ Leuven, Univ Hosp, Dept Pathol, GI Pathol Unit, B-3000 Louvain, Belgium

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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Bates, DM
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Bolstad, B
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Dudoit, S
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

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Gautier, L
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Hornik, K
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Hothorn, T
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Huber, W
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Iacus, S
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Irizarry, R
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Leisch, F
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Li, C
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Maechler, M
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Rossini, AJ
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Sawitzki, G
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Smith, C
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Smyth, G
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Tierney, L
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Yang, JYH
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA

Zhang, JH
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机构: Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA