Schaeffer C, Diab-Assef M, Plateroti M, Laurent-Huck F, Reimund J M, Kedinger M, Foltzer-Jourdainne C
INSERM U381, Strasbourg, France.
Gut. 2000 Aug;47(2):192-8. doi: 10.1136/gut.47.2.192.
In the intestinal mucosa, numerous cytokines produced by the epithelium, fibroblasts, and immune cells were shown to affect epithelial differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interactions. To date, the importance of cytokines in postnatal development of the rat small intestine has not been established.
To investigate the developmental changes in expression of mucosal cytokines in the postnatal maturation of the rat small intestinal epithelium and their regulation by glucocorticoids (GC).
Mucosal maturation was assessed by the onset of sucrase-isomaltase (SI) mRNA, analysed by in situ hybridisation. The amount of transforming growth factor beta1 (TGF-beta1), beta2 (TGF-beta2), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and TGF-alpha was analysed by reverse transcription-polymerase chain reaction (RT-PCR) in mucosal extracts from weaning (14-21 days old) and adult rats, or one day after an injection of hydrocortisone (HC) in 11 day old rats. Similarly, expression of cytokines and the regulatory effect of GC were studied on cultured subepithelial myofibroblasts cloned from postnatal jejunum and ileum cultured in the absence or presence of dexamethasone (DX).
TGF-beta1, TGF-beta2, and IL-1beta decreased during the third week of life while levels of TNF-alpha increased and TGF-alpha remained constant. In parallel, SI transcripts increased and showed a progressive accumulation in the apical part of the enterocytes first localised at the base of the villi from 18 days onwards. Interestingly, precocious induction of SI mRNA by HC paralleled the decrease in expression of TGF-beta isoforms and of IL-1beta. All cytokines were expressed in the myofibroblast cell lines. In addition, the results showed that TNF-alpha was differentially expressed in basal culture conditions and after DX stimulation in jejunal and ileal myofibroblasts. DX decreased IL-1beta but not the TGF-beta isoforms, similar to that in vivo.
This study shows that mucosal cytokines are developmentally regulated and that GC are potentially involved in this regulation in parallel with maturation of the gut mucosa at weaning.
在肠黏膜中，上皮细胞、成纤维细胞和免疫细胞产生的多种细胞因子通过上皮-间充质及上皮-免疫细胞相互作用影响上皮细胞的分化和增殖。迄今为止，细胞因子在大鼠小肠出生后发育中的重要性尚未明确。
研究大鼠小肠上皮细胞出生后成熟过程中黏膜细胞因子表达的发育变化及其受糖皮质激素（GC）的调节。
通过蔗糖酶-异麦芽糖酶（SI）mRNA的出现来评估黏膜成熟度，采用原位杂交法进行分析。采用逆转录-聚合酶链反应（RT-PCR）分析断奶（14 - 21日龄）和成年大鼠黏膜提取物中转化生长因子β1（TGF-β1）、β2（TGF-β2）、肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）和TGF-α的含量，或分析11日龄大鼠注射氢化可的松（HC）一天后的上述指标。同样，研究细胞因子的表达及GC对从出生后空肠和回肠克隆的培养上皮下肌成纤维细胞的调节作用，培养时分别添加或不添加地塞米松（DX）。
TGF-β1、TGF-β2和IL-1β在出生后第三周含量下降，而TNF-α水平升高，TGF-α保持稳定。与此同时，SI转录本增加，并从18日龄起在首先位于绒毛底部的肠上皮细胞顶端部分逐渐积累。有趣的是，HC对SI mRNA的早熟诱导与TGF-β亚型和IL-1β表达的降低同时出现。所有细胞因子均在肌成纤维细胞系中表达。此外，结果显示TNF-α在空肠和回肠肌成纤维细胞的基础培养条件下及DX刺激后表达存在差异。DX降低了IL-1β，但不影响TGF-β亚型，这与体内情况相似。
本研究表明黏膜细胞因子受发育调控，且GC可能在断奶时肠道黏膜成熟的同时参与这一调控过程。
