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Prominent Indomethacin-Induced Enteropathy in Fcgriib
- Source :
- International Journal of Molecular Sciences
- Publication Year :
- 2020
-
Abstract
- A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, an asymptomatic lupus model (increased anti-dsDNA without lupus nephritis), and age-matched wild-type (WT) mice. Severity of indomethacin-induced enteropathy in FcgRIIb-/- mice was higher than WT mice as demonstrated by survival analysis, intestinal injury (histology, immune-deposition, and intestinal cytokines), gut leakage (FITC-dextran assay and endotoxemia), serum cytokines, and lupus characteristics (anti-dsDNA, renal injury, and proteinuria). Prominent responses of FcgRIIb-/- macrophages toward lipopolysaccharide (LPS) compared to WT cells due to the expression of only activating-FcgRs without inhibitory-FcgRIIb were demonstrated. Extracellular flux analysis indicated the greater mitochondria activity (increased respiratory capacity and respiratory reserve) in FcgRIIb-/- macrophages with a concordant decrease in glycolysis activity when compared to WT cells. In conclusion, gut leakage-induced endotoxemia is more severe in indomethacin-administered FcgRIIb-/- mice than WT, possibly due to the enhanced indomethacin toxicity from lupus-induced intestinal immune-deposition. Due to a lack of inhibitory-FcgRIIb expression, mitochondrial function, and cytokine production of FcgRIIb-/- macrophages were more prominent than WT cells. Hence, lupus disease-activation from NSAIDs-enteropathy-induced gut leakage is possible.
- Subjects :
- Enterocolitis
Macrophages
Anti-Inflammatory Agents, Non-Steroidal
Indomethacin
Receptors, IgG
Macrophage Activation
Endotoxemia
Article
gut leakage
Mice, Inbred C57BL
NSAIDs-enteropathy
Disease Models, Animal
systemic lupus erythematosus
FcgRIIb deficient mice
Animals
Lupus Erythematosus, Systemic
Female
skin and connective tissue diseases
Gene Deletion
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.pmid..........88a3900f255fb66f1843bac3ae0c0a65