Instituto de Estudios Inmunologicos y Fisiopatologicos IIFP (UNLP-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Instituto de Estudios Inmunologicos y Fisiopatologicos IIFP (UNLP-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Immunol Lett. 2022 Dec;251-252:56-62. doi: 10.1016/j.imlet.2022.10.006. Epub 2022 Oct 27.
The intestinal mucosa is covered by a layer of epithelial cells that is constantly challenged by commensal, opportunistic, and pathogenic microorganisms, their components, and harmful compounds. Any inflammatory response to these materials must be tightly controlled to limit tissue damage and restore the integrity of the mucosal barrier. We have shown previously that production of IL-1β via activation of the inflammasome can lead to mucosal damage in the small intestinal pathology that occurs after intragastric administration of a gluten derived peptide, p31-43. Here we show that specific inhibition of caspase-1 or NLRP3 abolishes the damage induced by p31-43, and that antibody-mediated blocking of IL-1β inhibits the both the histological changes and the induction of apoptosis and caspase-3 activation driven by p31-43. Understanding the role of IL-1β in sterile inflammation may help to understand chronic inflammatory pathological processes, and design new intervention strategies.
肠黏膜被一层上皮细胞覆盖，这些细胞不断受到共生菌、机会致病菌和致病菌及其成分和有害化合物的挑战。任何对这些物质的炎症反应都必须受到严格控制，以限制组织损伤并恢复黏膜屏障的完整性。我们之前已经表明，通过激活炎性小体产生的 IL-1β 可导致在胃内给予源自面筋的肽 p31-43 后发生的小肠病理学中的黏膜损伤。在这里，我们表明 caspase-1 或 NLRP3 的特异性抑制可消除 p31-43 诱导的损伤，并且抗体介导的 IL-1β 阻断可抑制 p31-43 驱动的组织学变化以及细胞凋亡和 caspase-3 激活的诱导。了解 IL-1β 在无菌性炎症中的作用可能有助于理解慢性炎症性病理过程，并设计新的干预策略。
