Wehkamp Jan, Schauber Jürgen, Stange Eduard F
Robert Bosch Hospital, Stuttgart, Germany.
Curr Opin Gastroenterol. 2007 Jan;23(1):32-8. doi: 10.1097/MOG.0b013e32801182c2.
To review recently published studies presenting novel and relevant information on antimicrobial peptides in gastrointestinal infections.
Defensins and cathelicidins are important antimicrobial peptides expressed by the gastrointestinal epithelium. Their localization and regulation have been the focus of current research establishing the relevance of these peptides both in counteracting an attack by pathogens as well as in controlling the endogenous bacterial flora. In the small intestine, Paneth cell alpha-defensins maintain a low level of microorganisms and regulate the composition of the bacterial flora. In contrast, a constitutive beta-defensin can be found in nearly all gastrointestinal tissues. Other relevant beta-defensins as well as human cathelicidin are inducible by inflammation or infections. Thus Helicobacter pylori enhances defensin expression in the gastric mucosa and Campylobacter jejuni and Salmonella provoke a similar response in the colon. Other pathogenic bacteria may suppress the antimicrobial peptide response as an escape strategy. Notably, the therapeutic induction of cathelicidins alleviates experimental shigellosis, suggesting a future role of endogenous antibiotics in medical therapy.
These recent findings together with a better understanding of underlying mechanisms involved in the regulation and biology of antimicrobial peptides will open up new therapeutic avenues to battle infections.
回顾近期发表的关于胃肠道感染中抗菌肽的新颖且相关信息的研究。
防御素和cathelicidins是胃肠道上皮表达的重要抗菌肽。它们的定位和调控一直是当前研究的重点,这些研究确立了这些肽在抵抗病原体攻击以及控制内源性细菌菌群方面的相关性。在小肠中,潘氏细胞α -防御素维持低水平的微生物并调节细菌菌群的组成。相比之下,几乎所有胃肠道组织中都可发现组成性β -防御素。其他相关的β -防御素以及人cathelicidin可由炎症或感染诱导产生。因此,幽门螺杆菌可增强胃黏膜中防御素的表达,空肠弯曲菌和沙门氏菌可在结肠引发类似反应。其他病原菌可能会抑制抗菌肽反应作为一种逃避策略。值得注意的是,cathelicidins的治疗性诱导可减轻实验性志贺氏菌病,这表明内源性抗生素在医学治疗中具有未来应用前景。
这些最新发现以及对抗菌肽调控和生物学潜在机制的更好理解将为对抗感染开辟新的治疗途径。