New insights in gut-liver axis in wild-type murine imiquimod-induced lupus

• Published in: Lupus Vol. 30; no. 6; pp. 926 - 936
• Main Authors: Maalouly, Georges, Hajal, Joelle, Noujeim, Charbel, Choueiry, Michel, Nassereddine, Hussein, Smayra, Viviane, Saliba, Youakim, Fares, Nassim
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2021; Sage Publications Ltd
• Subjects: Antiviral drugs; Digestive system; E coli; Feces; Gastrointestinal tract; Imiquimod; Inflammation; Intestine; Liver; Liver diseases; Lupus; Lupus nephritis; Nephritis; NF-κB protein; Permeability; Proteins; TLR4 protein; TLR7 protein; Toll-like receptors; Zonula occludens-1 protein; Lupus; TLR; gut permeability; mice; calprotectin; imiquimod
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203321995254

Background 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. Objective This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus. Methods 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 E. coli protein in liver were assessed at sacrifice. Results 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. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression. Conclusion 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.