Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
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 (FcgRII...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1377 |
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| author | Thansita Bhunyakarnjanarat Kanyarat Udompornpitak Wilasinee Saisorn Bhumdhanin Chantraprapawat Peerapat Visitchanakun Cong Phi Dang Jiraphorn Issara-Amphorn Asada Leelahavanichkul |
| author_facet | Thansita Bhunyakarnjanarat Kanyarat Udompornpitak Wilasinee Saisorn Bhumdhanin Chantraprapawat Peerapat Visitchanakun Cong Phi Dang Jiraphorn Issara-Amphorn Asada Leelahavanichkul |
| author_sort | Thansita Bhunyakarnjanarat |
| collection | DOAJ |
| description | 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-<i>FcgRIIb</i> 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-<i>FcgRIIb</i> 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. |
| first_indexed | 2024-03-09T03:17:27Z |
| format | Article |
| id | doaj.art-f0711aa3d30d4b49a715818bc63c70f7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:17:27Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f0711aa3d30d4b49a715818bc63c70f72023-12-03T15:18:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223137710.3390/ijms22031377Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in GutThansita Bhunyakarnjanarat0Kanyarat Udompornpitak1Wilasinee Saisorn2Bhumdhanin Chantraprapawat3Peerapat Visitchanakun4Cong Phi Dang5Jiraphorn Issara-Amphorn6Asada Leelahavanichkul7Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandTranslational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandA 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-<i>FcgRIIb</i> 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-<i>FcgRIIb</i> 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.https://www.mdpi.com/1422-0067/22/3/1377FcgRIIb deficient micesystemic lupus erythematosusNSAIDs-enteropathygut leakage |
| spellingShingle | Thansita Bhunyakarnjanarat Kanyarat Udompornpitak Wilasinee Saisorn Bhumdhanin Chantraprapawat Peerapat Visitchanakun Cong Phi Dang Jiraphorn Issara-Amphorn Asada Leelahavanichkul Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut International Journal of Molecular Sciences FcgRIIb deficient mice systemic lupus erythematosus NSAIDs-enteropathy gut leakage |
| title | Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut |
| title_full | Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut |
| title_fullStr | Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut |
| title_full_unstemmed | Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut |
| title_short | Prominent Indomethacin-Induced Enteropathy in Fcgriib <i>Defi-cient lupus</i> Mice: An Impact of Macrophage Responses and Immune Deposition in Gut |
| title_sort | prominent indomethacin induced enteropathy in fcgriib i defi cient lupus i mice an impact of macrophage responses and immune deposition in gut |
| topic | FcgRIIb deficient mice systemic lupus erythematosus NSAIDs-enteropathy gut leakage |
| url | https://www.mdpi.com/1422-0067/22/3/1377 |
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