Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
| Autor: | Peerapat Visitchanakun, Bhumdhanin Chantraprapawat, Wilasinee Saisorn, Asada Leelahavanichkul, Cong Phi Dang, Jiraphorn Issara-Amphorn, Thansita Bhunyakarnjanarat, Kanyarat Udompornpitak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Lipopolysaccharide medicine.medical_treatment Lupus nephritis Catalysis gut leakage Inorganic Chemistry lcsh:Chemistry NSAIDs-enteropathy chemistry.chemical_compound Immune system systemic lupus erythematosus Internal medicine FcgRIIb deficient mice medicine Macrophage Enteropathy Physical and Theoretical Chemistry skin and connective tissue diseases Molecular Biology lcsh:QH301-705.5 Spectroscopy Systemic lupus erythematosus business.industry Organic Chemistry General Medicine medicine.disease Computer Science Applications Endocrinology Cytokine chemistry lcsh:Biology (General) lcsh:QD1-999 Toxicity business |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 3 International Journal of Molecular Sciences, Vol 22, Iss 1377, p 1377 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22031377 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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