Donnarumma Giovanna, Paoletti Iole, Fusco Alessandra, Perfetto Brunella, Buommino Elisabetta, de Gregorio Vincenza, Baroni Adone
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, via De Crecchio n°7, 80138, Naples, Italy.
Center for Advanced Biomaterial for Health Care Technology, Italian Institute of Technology, Largo Barsanti E Matteucci 53, 80125, Naples, Italy.
Adv Exp Med Biol. 2016;901:59-76. doi: 10.1007/5584_2015_5016.
Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The increase in the resistance of bacteria to conventional antibiotics and the need for new antibiotics has stimulated interest in the use of AMPs as new therapeutic agents. The inducible nature of human defensin genes suggests that it is possible to increase the endogenous production by utilizing small molecules of various origins to enhance, even selectively, the expression of these peptides. In the light of their role in immunomodulation, angiogenesis, wound healing, inflammation and cancer, as well as their antimicrobial activity, it is possible induce their expression or create analogs with increased specific activity or various degrees of selectivity, or obtain human defensins with genetic engineering to optimize the potency and safety in order to reduce cytotoxicity and potential proinflammatory activity and susceptibility to protease and salt. Restoring the balance between immunostimulating and immunosuppressive molecules may be an important strategy to correct expression defects in specific diseases.
防御素是在不同生物体中发现的一类抗菌肽(AMPs),参与针对病原体的固有免疫反应的第一道防线。细菌对传统抗生素耐药性的增加以及对新型抗生素的需求,激发了人们对将抗菌肽用作新型治疗剂的兴趣。人类防御素基因的可诱导特性表明,利用各种来源的小分子来增强甚至选择性地增强这些肽的表达,从而增加内源性产量是可能的。鉴于它们在免疫调节、血管生成、伤口愈合、炎症和癌症中的作用,以及它们的抗菌活性,可以诱导它们的表达或创造具有更高比活性或不同程度选择性的类似物,或者通过基因工程获得人类防御素,以优化效力和安全性,从而降低细胞毒性、潜在的促炎活性以及对蛋白酶和盐的敏感性。恢复免疫刺激分子和免疫抑制分子之间的平衡可能是纠正特定疾病中表达缺陷的重要策略。