IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III - Paul Sabatier (UPS), Toulouse, France.
Université Paris-Saclay, AgroParisTech, Micalis Institute, INRAE, Jouy-en-Josas, France.
Br J Pharmacol. 2023 Jan;180(2):144-160. doi: 10.1111/bph.15985. Epub 2022 Nov 28.
Elafin and its precursor trappin-2 are known for their contribution to the physiological mucosal shield against luminal microbes. Such a contribution seems to be particularly relevant in the gut, where the exposure of host tissues to heavy loads of microbes is constant and contributes to mucosa-associated pathologies. The expression of trappin-2/elafin has been shown to be differentially regulated in diseases associated with gut inflammation. Accumulating evidence has demonstrated the protective effects of trappin-2/elafin in gut intestinal disorders associated with acute or chronic inflammation, or with gluten sensitization disorders. The protective effects of trappin-2/elafin in the gut are discussed in terms of their pleiotropic modes of action: acting as protease inhibitors, transglutaminase substrates, antimicrobial peptides or as a regulator of pro-inflammatory transcription factors. Further, the question of the therapeutic potential of trappin-2/elafin delivery at the intestinal mucosa surface is raised. Whether trappin-2/elafin mucosal delivery should be considered to ensure intestinal tissue repair is also discussed.
Elafin 和其前体 trappin-2 以其对生理黏膜屏障抵御腔道微生物的贡献而闻名。这种贡献在肠道中似乎尤为重要,因为宿主组织不断暴露于大量微生物中,这导致了与黏膜相关的疾病。已经表明,trappin-2/elafin 的表达在与肠道炎症相关的疾病中受到差异调控。越来越多的证据表明,trappin-2/elafin 对与急性或慢性炎症或麸质致敏紊乱相关的肠道肠道疾病具有保护作用。讨论了 trappin-2/elafin 在肠道中的保护作用,涉及到其多效作用模式:作为蛋白酶抑制剂、转谷氨酰胺酶底物、抗菌肽或作为促炎转录因子的调节剂。此外,还提出了在肠黏膜表面递送 trappin-2/elafin 的治疗潜力问题。是否应考虑 trappin-2/elafin 黏膜递送以确保肠道组织修复也进行了讨论。