Lueschow-Guijosa Shiloh R, Stanford Amy H, Berger Jennifer N, Gong Huiyu, Boly Timothy J, Jensen Benjamin A H, Nordkild Peter, Leegwater Alexandra J, Wehkamp Jan, Underwood Mark A, McElroy Steven J
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Department of Pediatrics, Children's Minnesota, Minneapolis, MN 55404, USA.
iScience. 2024 May 15;27(6):109993. doi: 10.1016/j.isci.2024.109993. eCollection 2024 Jun 21.
Necrotizing enterocolitis (NEC) is a leading cause of preterm infant morbidity and mortality. Treatment for NEC is limited and non-targeted, which makes new treatment and prevention strategies critical. Host defense peptides (HDPs) are essential components of the innate immune system and have multifactorial mechanisms in host defense. LL-37 and hBD2 are two HDPs that have been shown in prior literature to protect from neonatal sepsis-induced mortality or adult inflammatory bowel disease, respectively. Therefore, this article sought to understand if these two HDPs could influence NEC severity in murine preclinical models. NEC was induced in P14-16 C57Bl/6 mice and HDPs were provided as a pretreatment or treatment. Both LL-37 and hBD2 resulted in decreased NEC injury scores as a treatment and hBD2 as a pretreatment. Our data suggest LL-37 functions through antimicrobial properties, while hBD2 functions through decreases in inflammation and improvement of intestinal barrier integrity.
坏死性小肠结肠炎（NEC）是早产婴儿发病和死亡的主要原因。NEC的治疗方法有限且缺乏针对性，这使得新的治疗和预防策略至关重要。宿主防御肽（HDPs）是先天免疫系统的重要组成部分，在宿主防御中具有多因素机制。LL-37和hBD2是两种HDPs，先前的文献表明它们分别可预防新生儿败血症诱导的死亡或成人炎症性肠病。因此，本文旨在了解这两种HDPs是否会影响小鼠临床前模型中的NEC严重程度。在P14-16 C57Bl/6小鼠中诱导NEC，并将HDPs作为预处理或治疗手段。LL-37和hBD2作为治疗手段均能降低NEC损伤评分，hBD2作为预处理也有此效果。我们的数据表明，LL-37通过抗菌特性发挥作用，而hBD2则通过减轻炎症和改善肠道屏障完整性发挥作用。
