Schauber Jürgen, Dorschner Robert A, Yamasaki Kenshi, Brouha Brook, Gallo Richard L
Division of Dermatology, University of California, San Diego and VA San Diego Healthcare System, San Diego, CA, USA.
Immunology. 2006 Aug;118(4):509-19. doi: 10.1111/j.1365-2567.2006.02399.x.
Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and beta-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia but not in keratinocytes or monocytes. Distinct factors induced beta-defensin expression. In all cell types, vitamin D3 activated the cathelicidin promoter and was dependent on a functional vitamin D responsive element. However, in colonic epithelia butyrate induced cathelicidin expression without increasing promoter activity and vitamin D3 activated the cathelicidin promoter without a subsequent increase in transcript accumulation. Induction of cathelicidin transcript correlated with increased processed mature peptide and enhanced antimicrobial activity against Staphylococcus aureus. However, induction of beta-defensin-2 expression did not alter the innate antimicrobial capacity of cells in culture. These data suggest that antimicrobial peptide expression is regulated in a tissue-specific manner at transcriptional, post-transcriptional and post-translational levels. Furthermore, these data show for the first time that innate antimicrobial activity can be triggered independently of the release of other pro-inflammatory molecules, and suggest strategies for augmenting innate immune defence without increasing inflammation.
机体对微生物的免疫防御部分依赖于抗菌肽的产生，这一过程发生在多种细胞类型中，但目前尚未完全了解。在本研究中，发现负责诱导cathelicidin和β-防御素抗菌肽的机制是独立的，且特定于细胞类型和刺激因素。维生素D3可诱导角质形成细胞和单核细胞中cathelicidin的表达，但在结肠上皮细胞中则不然。相反，丁酸盐可诱导结肠上皮细胞中cathelicidin的表达，但在角质形成细胞或单核细胞中则无此作用。不同的因素可诱导β-防御素的表达。在所有细胞类型中，维生素D3均可激活cathelicidin启动子，且依赖于功能性维生素D反应元件。然而，在结肠上皮细胞中，丁酸盐可诱导cathelicidin表达而不增加启动子活性，维生素D3可激活cathelicidin启动子但随后转录物积累并无增加。cathelicidin转录物的诱导与加工成熟肽的增加以及对金黄色葡萄球菌抗菌活性的增强相关。然而，β-防御素-2表达的诱导并未改变培养细胞的固有抗菌能力。这些数据表明，抗菌肽的表达在转录、转录后和翻译后水平上以组织特异性方式受到调节。此外，这些数据首次表明，固有抗菌活性可独立于其他促炎分子的释放而被触发，并提出了在不增加炎症的情况下增强固有免疫防御的策略。
