Departments of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
J Leukoc Biol. 2012 Oct;92(4):735-42. doi: 10.1189/jlb.0412178. Epub 2012 Jun 13.
As traditional antibiotics gradually become inefficient, there is a high demand for development of anti-infectives with a mechanism of action that is different from existing antibiotics. Current antibiotics target the pathogen directly, thereby contributing to the selection of multidrug-resistant bacterial strains. AMPs, such as the human cathelicidin LL-37, are small cationic peptides that are part of host defense. They eliminate microbes through diverse mechanisms, thereby contributing to resolution of infections and maintenance of epithelial barrier function. The multiplicity of these mechanisms of action might be a key to restrict the development of resistant bacterial strains. The discovery of LL-37-inducing components, such as butyrate and vitamin D(3), has opened new avenues to prevent or treat infections. Butyrate and vitamin D(3) are potent inducers of LL-37 but in addition, have many other effects on host immunity. Here, we summarize current data on the effects that LL-37 and its inducers display on the innate immune response and discuss the feasibility for development of these inducers as possible drugs to prevent or treat infections.
随着传统抗生素逐渐失效，人们迫切需要开发作用机制不同于现有抗生素的抗感染药物。目前的抗生素直接针对病原体，从而促进了多药耐药菌株的选择。抗菌肽（AMPs），如人源防御素 LL-37，是宿主防御的一部分，它们是小阳离子肽。它们通过多种机制消除微生物，从而有助于解决感染并维持上皮屏障功能。这些作用机制的多样性可能是限制耐药菌株发展的关键。发现 LL-37 诱导成分，如丁酸盐和维生素 D(3)，为预防或治疗感染开辟了新途径。丁酸盐和维生素 D(3)是 LL-37 的有效诱导剂，但除此之外，它们对宿主免疫还有许多其他影响。在这里，我们总结了关于 LL-37 及其诱导剂对先天免疫反应的影响的最新数据，并讨论了将这些诱导剂开发为预防或治疗感染的潜在药物的可行性。
