Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60610, USA.
Clin Exp Allergy. 2010 Mar;40(3):427-34. doi: 10.1111/j.1365-2222.2009.03419.x. Epub 2009 Dec 16.
Eosinophilic oesophagitis (EE) is a clinico-pathologically defined oesophageal disorder that is characterized by eosinophil migration into oesophageal tissues. There is growing support for EE being an allergic disease and for a contribution of T-helper type 2 (Th2)-associated cytokines in disease pathogenesis. The respiratory system has been shown to be critical in driving the development of EE in animal models. However, the mechanisms underlying the recruitment of eosinophils into the oesophagus remain unclear.
We sought to investigate the influence of Th2-associated cytokines on the production of eosinophil-specific chemokines from the oesophagus directly.
In order to eliminate the potential involvement of the lung, we utilized isolated oesophageal rings. These were treated in vitro with IL-4 or IL-13 and the expression and production of CCL11 and CCL24 were determined.
Our data demonstrate that IL-13 is a potent and direct inducer of both CCL11 and CCL24 production from the oesophagus, as is IL-4 also. The expression of CCL11 precedes CCL24 by several hours but then diminishes over time, as well as at high concentrations of IL-13. We demonstrate that there is an up-regulation of the inhibitory IL-13 receptor, IL-13Ralpha2 but that IL-13Ralpha1 remains unaltered. Oesophagus rings isolated from STAT6(-/-) mice were unable to produce CCL11 or CCL24 upon IL-13 treatment. Lastly, we demonstrate that oesophageal production of CCL11 and CCL24 upon IL-13 stimulation is sufficient to promote eosinophil migration.
IL-13 is capable of directly stimulating oesophageal tissue to produce eosinophil-attracting chemokines and drive eosinophil migration.
嗜酸性食管炎（EE）是一种临床病理定义明确的食管疾病，其特征是嗜酸性粒细胞迁移到食管组织中。越来越多的证据支持 EE 是一种过敏性疾病，并且 Th2 相关细胞因子在疾病发病机制中起作用。呼吸系统在动物模型中被证明对 EE 的发展至关重要。然而，嗜酸性粒细胞招募到食管中的机制仍不清楚。
我们试图直接研究 Th2 相关细胞因子对食管产生嗜酸性粒细胞特异性趋化因子的影响。
为了消除肺部的潜在参与，我们使用分离的食管环。这些食管环在体外用 IL-4 或 IL-13 处理，并确定 CCL11 和 CCL24 的表达和产生。
我们的数据表明，IL-13 是食管中 CCL11 和 CCL24 产生的有力和直接诱导剂，IL-4 也是如此。CCL11 的表达先于 CCL24 几个小时，但随着时间的推移而减少，并且在高浓度的 IL-13 时也会减少。我们证明存在抑制性 IL-13 受体 IL-13Ralpha2 的上调，但 IL-13Ralpha1 保持不变。在 IL-13 处理时，来自 STAT6(-/-) 小鼠的食管环无法产生 CCL11 或 CCL24。最后，我们证明 IL-13 刺激食管产生 CCL11 和 CCL24 足以促进嗜酸性粒细胞迁移。
IL-13 能够直接刺激食管组织产生吸引嗜酸性粒细胞的趋化因子，并驱动嗜酸性粒细胞迁移。
