Faculty of Medicine, CHU Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon.
Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
Lupus. 2021 May;30(6):926-936. doi: 10.1177/0961203321995254. Epub 2021 Feb 17.
Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated.
This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus.
C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and protein in liver were assessed at sacrifice.
At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression.
This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.
与其他主要器官损伤相比，狼疮的肠道和肝脏表现似乎被低估了。尽管最近的数据指出肠道-肝脏轴在狼疮中受累，但肠道通透性功能障碍和肝脏炎症需要进一步研究。
本研究旨在评估野生型咪喹莫特诱导狼疮小鼠的粪便钙卫蛋白、肠道紧密连接蛋白和肝脏炎症通路。
将 C57BL/6 小鼠右侧耳部每周三次用 1.25mg 5%咪喹莫特乳膏进行局部处理，共 6 周。在第 0、22 和 45 天收集粪便钙卫蛋白。在处死时评估肾脏、肝脏和肠道病理学以及炎症标志物、肠道紧密连接蛋白和肝脏中的蛋白。
在 6 周时，通过组织病理学证实狼疮肾炎和 NGAL 和 KIM-1 的表达。钙卫蛋白的升高始于第 22 天，并持续到第 45 天。Claudine、ZO-1 和 occludin 的蛋白表达明显降低。肝脏中存在坏死性炎症，TLR4、TLR7 和 pNFκB/NFκB 肝脏表达增加，蛋白表达显著增加。
本研究首次证明了野生型咪喹莫特诱导狼疮小鼠粪便钙卫蛋白早期增加和肝脏 TLR4-NFκB 通路的激活。
