Moro F, Levenez F, Durual S, Plaisancié P, Thim L, Giraud A S, Cuber J C
Inserm Unité 45, Hôpital Edouard-Herriot, Pavillon Hbis, 69437 Cedex 03, Lyon, France.
Regul Pept. 2001 Sep 15;101(1-3):35-41. doi: 10.1016/s0167-0115(01)00257-9.
The trefoil factor TFF3 is a peptide predominantly produced by mucus-secreting cells in the small and large intestines. It has been implicated in intestinal protection and repair. The mechanisms that govern TFF3 secretion are poorly understood. The aim of this study was, therefore, to evaluate the influence of neurotransmitters, hormonal peptides and mediators of inflammation on the release of TFF3. For this purpose, an isolated vascularly perfused rat colon preparation was used. After a bolus administration of 1 ml isotonic saline into the lumen, TFF3 secretion was induced by a 30-min intra-arterial infusion of the compounds to be tested. TFF3 was evaluated in the luminal effluent using a newly developed radioimmunoassay. TFF3 was barely detected in crude luminal samples. In contrast, dithiothreitol (DTT) treatment of the effluent revealed TFF3 immunoreactivity, which amounted to about 0.3 pmol min(-1) cm(-1) in the basal state. Gel chromatography of DTT-treated luminal samples revealed a single peak that co-eluted with the monomeric form of TFF3. TFF3 was not detected in the portal effluent. Bethanechol (10(-6)-10(-4) M), vasoactive intestinal peptide (VIP, 10(-8)-10(-7) M) or bombesin (10(-8)-10(-7) M) induced a dose-dependent release of TFF3. In contrast, substance P evoked a modest release of TFF3, whereas calcitonin gene-related peptide (CGRP), somatostatin, neurotensin or peptide YY (PYY) did not modify TFF3 secretion. The degranulator compound bromolasalocid, 16,16-dimethyl PGE2 (dmPGE2) or interleukin-1-beta (IL-1-beta) also evoked a marked release of TFF3. In conclusion, TFF3 in the colonic effluent is present in a complex. This association presumably involves a disulfide bond. Additionally, the present results suggest a role for enteric nervous system and resident immune cells in mediation of colonic TFF3 secretion.
三叶因子TFF3是一种主要由小肠和大肠中分泌黏液的细胞产生的肽。它与肠道保护和修复有关。目前对TFF3分泌的调控机制了解甚少。因此，本研究的目的是评估神经递质、激素肽和炎症介质对TFF3释放的影响。为此，使用了离体血管灌注大鼠结肠标本。向肠腔内一次性注射1 ml等渗盐水后，通过对受试化合物进行30分钟的动脉内输注来诱导TFF3分泌。使用新开发的放射免疫分析法对肠腔流出物中的TFF3进行评估。在粗制的肠腔样本中几乎检测不到TFF3。相反，对流出物进行二硫苏糖醇（DTT）处理后显示出TFF3免疫反应性，在基础状态下约为0.3 pmol min(-1) cm(-1)。对经DTT处理的肠腔样本进行凝胶色谱分析，显示出一个与TFF3单体形式共洗脱的单峰。在门静脉流出物中未检测到TFF3。氨甲酰甲胆碱（10(-6)-10(-4) M）、血管活性肠肽（VIP，10(-8)-10(-7) M）或蛙皮素（10(-8)-10(-7) M）可诱导TFF3呈剂量依赖性释放。相反，P物质引起TFF3适度释放，而降钙素基因相关肽（CGRP）、生长抑素、神经降压素或肽YY（PYY）则不改变TFF3分泌。脱颗粒化合物溴氯杀鼠灵、16,16-二甲基前列腺素E2（dmPGE2）或白细胞介素-1-β（IL-1-β）也可引起TFF3显著释放。总之，结肠流出物中的TFF3以复合物形式存在。这种结合可能涉及二硫键。此外，目前的结果表明肠神经系统和常驻免疫细胞在结肠TFF3分泌的介导中起作用。
