Coordinate Interaction between IL-13 and Epithelial Differentiation Cluster Genes in Eosinophilic Esophagitis

被引：218

作者：

Blanchard, Carine ^{[1
]}

Stucke, Emily M. ^{[1
]}

Burwinkel, Karen ^{[1
]}

Caldwell, Julie M. ^{[1
]}

Collins, Margaret H. ^{[2
]}

Ahrens, Annette ^{[1
]}

Buckmeier, Bridget K. ^{[1
]}

Jameson, Sean C. ^{[1
]}

Greenberg, Allison ^{[1
]}

Kaul, Ajay ^{[3
]}

Franciosi, James P. ^{[3
]}

Kushner, Jonathan P. ^{[4
]}

Martin, Lisa J. ^{[5
,6
]}

Putnam, Philip E. ^{[3
]}

Abonia, J. Pablo ^{[1
]}

Wells, Suzanne I. ^{[1
,7
]}

Rothenberg, Marc E. ^{[1
,5
,6
]}

机构：

[1] Univ Cincinnati, Med Ctr, Div Allergy & Immunol, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Med Ctr, Div Pathol & Lab Med, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[3] Univ Cincinnati, Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[4] Univ Cincinnati, Med Ctr, Div Gastroenterol, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[5] Univ Cincinnati, Med Ctr, Div Biostat & Epidemiol, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[6] Univ Cincinnati, Med Ctr, Div Human Genet, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

[7] Univ Cincinnati, Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati Childrens Hosp,Coll Med,Dept Pediat, Cincinnati, OH 45229 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 07期

基金：

美国国家卫生研究院;

关键词：

RECONSTRUCTED HUMAN EPIDERMIS; HUMAN INVOLUCRIN GENE; OF-FUNCTION MUTATIONS; SKIN BARRIER FUNCTION; FILAGGRIN MUTATIONS; ATOPIC-DERMATITIS; TRANSGENIC MICE; EXPRESSION; EOTAXIN-3; COMPLEX;

D O I：

10.4049/jimmunol.0903069

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We have previously proposed that the pathogenesis of eosinophilic esophagitis (EE) is mediated by an IL-13-driven epithelial cell response associated with marked gene dysregulation including eotaxin-3 overproduction. In this study, we compared epithelial responses between healthy patients and those with EE, aiming to uncover molecular explanations for EE pathogenesis. Esophageal epithelial cells could be maintained for up to five passages, with 67% and 62% of cell lines reaching confluence in healthy controls and EE cases, respectively. Both sets of epithelial cells avidly responded to IL-13 at similar levels as assessed by eotaxin-3 production. Acidic pH increased cellular release of eotaxin-3 (4.6 +/- 1.98 ng/ml versus 12.46 +/- 2.90 ng/ml at pH 7.4 and 4, respectively; p < 0.05). Numerous epidermal differentiation complex (EDC) genes, such as filaggrin and SPRR3, were down-regulated both in 11-13-stimulated esophageal epithelial cells and in EE biopsies specimens compared with healthy controls. Whereas the filaggrin loss of function mutation 2282de14 was overrepresented in EE compared with control individuals (6.1% versus 1.3% respectively; p = 0.0172), the decreased filaggrin expression was uniformly seen in all EE cases in vivo. Indeed, expression of the EDC genes filaggrin and involucrin was strongly decreased directly by IL-13. These results establish that the epithelial response in EE involves a cooperative interaction between 11,43 and expression of EDC genes. The Journal of Immunology, 2010, 184: 4033-4041.

引用

页码：4033 / 4041

页数：9

共 45 条

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