de Jonge Wouter J, Greaves David R
Laboratory of Experimental Gastroenterology and Hepatology, Academic Medical Center Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Expert Rev Gastroenterol Hepatol. 2008 Dec;2(6):741-8. doi: 10.1586/17474124.2.6.741.
Inflammation is the response of vascularized tissues to injury, irritation and infection. Nearly always, the inflammatory response is successfully resolved and, when necessary, a process of wound healing is initiated. Nowhere in the body is this homeostatic process more challenging than in the gastrointestinal (GI) tract, where the microbial flora sits in very close proximity to the mucosal immune system, separated only by an epithelial cell barrier. Delicate regulatory systems of the mucosal immune system determine mucosal permeability and response to bacterial flora, and aberrations in this system result in acute or chronic inflammatory conditions. Examples of such are two commonly occurring inflammatory GI disorders: inflammatory bowel disease and postoperative ileus. Inflammatory bowel disease is the result of a chronic and excessive mucosal immune response, whereas postoperative ileus represents a transient condition of GI tract paralysis that is the result of an inflammatory response to abdominal surgery. The clinical management of both conditions is very challenging and depends heavily on the possibility of modulating the host immune response. In this brief report, we highlight the role of neuropeptides in GI physiology and immune regulation, discuss a recently discovered endogenous anti-inflammatory pathway mediated by the ChemR23 receptor and speculate on the therapeutic potential of peptides that bind G-protein-coupled receptors in the management of inflammation in the GI tract.
炎症是血管化组织对损伤、刺激和感染的反应。几乎在所有情况下，炎症反应都能成功消退，必要时还会启动伤口愈合过程。在人体中，这种稳态过程在胃肠道面临的挑战最大，因为微生物菌群与黏膜免疫系统紧密相邻，仅由一层上皮细胞屏障分隔。黏膜免疫系统的精细调节系统决定了黏膜通透性以及对细菌菌群的反应，该系统的异常会导致急性或慢性炎症状态。常见的两种炎症性胃肠道疾病就是例证：炎症性肠病和术后肠梗阻。炎症性肠病是慢性且过度的黏膜免疫反应的结果；而术后肠梗阻则是胃肠道麻痹的一种短暂状态，是腹部手术引发炎症反应的结果。这两种病症的临床治疗都极具挑战性，且在很大程度上依赖于调节宿主免疫反应的可能性。在本简要报告中，我们着重阐述神经肽在胃肠道生理和免疫调节中的作用，讨论最近发现的由ChemR23受体介导的内源性抗炎途径，并推测与G蛋白偶联受体结合的肽在胃肠道炎症治疗中的潜力。
