Reinshagen M, Rohm H, Steinkamp M, Lieb K, Geerling I, Von Herbay A, Flämig G, Eysselein V E, Adler G
Department of Medicine I, University of Ulm, Ulm, Germany.
Gastroenterology. 2000 Aug;119(2):368-76. doi: 10.1053/gast.2000.9307.
BACKGROUND & AIMS: Sensory neuropeptides modulate the mucosal response to inflammation in experimental colitis. Because nerve growth factor (NGF) regulates the expression of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) and is implicated as a link between the nervous system and the immune system in the inflammatory process, we investigated the functional role of NGF and neurotrophin-3 during experimental colitis.
Immunoneutralizing antibodies specific for NGF and neurotrophin (NT)-3 were used to block their endogenous activity. Mild trinitrobenzene sulfonic acid (TNBS) colitis was induced, and damage scores were assessed after 1 week. Neuropeptide content in the colon and NT messenger RNA (mRNA) expression were determined.
The pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in the severity of the experimental inflammation as assessed by a macroscopic damage score, histologic ulceration score, and myeloperoxidase activity in the tissue. CGRP, but not substance P, contents in the colon were significantly reduced by NGF immunoneutralization. NGF mRNA was slightly up-regulated after NGF immunoneutralization, but NT-3 mRNA was unchanged by NT-3 immunoneutralization. CGRP mRNA was not significantly changed after 1 week of colitis by NGF or NT-3 immunoneutralization, whereas beta-preprotachykinin mRNA was up-regulated after immunoneutralization.
These findings suggest a regulatory role for NGF and NT-3 in experimental inflammation of the gut. This effect may be partly caused by the reduction of mucosal CGRP content caused by the NGF blockade.
感觉神经肽可调节实验性结肠炎中黏膜对炎症的反应。由于神经生长因子（NGF）可调节诸如P物质和降钙素基因相关肽（CGRP）等神经肽的表达，并且在炎症过程中被认为是神经系统与免疫系统之间的联系纽带，因此我们研究了NGF和神经营养因子-3在实验性结肠炎中的功能作用。
使用针对NGF和神经营养因子（NT）-3的免疫中和抗体来阻断其内源活性。诱导轻度三硝基苯磺酸（TNBS）结肠炎，并在1周后评估损伤评分。测定结肠中的神经肽含量和NT信使核糖核酸（mRNA）表达。
通过宏观损伤评分、组织学溃疡评分和组织中的髓过氧化物酶活性评估，用抗NGF或抗NT-3进行预处理导致实验性炎症的严重程度显著增加2至3倍。NGF免疫中和可使结肠中CGRP的含量显著降低，但P物质的含量未降低。NGF免疫中和后NGF mRNA略有上调，但NT-3免疫中和后NT-3 mRNA未发生变化。NGF或NT-3免疫中和1周的结肠炎后CGRP mRNA无显著变化，而免疫中和后β-前速激肽原mRNA上调。
这些发现表明NGF和NT-3在肠道实验性炎症中具有调节作用。这种作用可能部分是由NGF阻断导致黏膜CGRP含量降低引起的。
