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Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
by
Udompornpitak, Kanyarat
, Visitchanakun, Peerapat
, Issara-Amphorn, Jiraphorn
, Leelahavanichkul, Asada
, Saisorn, Wilasinee
, Dang, Cong Phi
, Bhunyakarnjanarat, Thansita
, Chantraprapawat, Bhumdhanin
in
Animals
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Disease Models, Animal
/ Endotoxemia - chemically induced
/ Endotoxemia - genetics
/ Endotoxemia - immunology
/ Enterocolitis - chemically induced
/ Enterocolitis - genetics
/ Enterocolitis - immunology
/ Female
/ Gene Deletion
/ Indomethacin - adverse effects
/ Lupus Erythematosus, Systemic - chemically induced
/ Lupus Erythematosus, Systemic - genetics
/ Lupus Erythematosus, Systemic - immunology
/ Macrophage Activation - drug effects
/ Macrophages - drug effects
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Receptors, IgG - genetics
/ Receptors, IgG - immunology
2021
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Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
by
Udompornpitak, Kanyarat
, Visitchanakun, Peerapat
, Issara-Amphorn, Jiraphorn
, Leelahavanichkul, Asada
, Saisorn, Wilasinee
, Dang, Cong Phi
, Bhunyakarnjanarat, Thansita
, Chantraprapawat, Bhumdhanin
in
Animals
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Disease Models, Animal
/ Endotoxemia - chemically induced
/ Endotoxemia - genetics
/ Endotoxemia - immunology
/ Enterocolitis - chemically induced
/ Enterocolitis - genetics
/ Enterocolitis - immunology
/ Female
/ Gene Deletion
/ Indomethacin - adverse effects
/ Lupus Erythematosus, Systemic - chemically induced
/ Lupus Erythematosus, Systemic - genetics
/ Lupus Erythematosus, Systemic - immunology
/ Macrophage Activation - drug effects
/ Macrophages - drug effects
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Receptors, IgG - genetics
/ Receptors, IgG - immunology
2021
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Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
by
Udompornpitak, Kanyarat
, Visitchanakun, Peerapat
, Issara-Amphorn, Jiraphorn
, Leelahavanichkul, Asada
, Saisorn, Wilasinee
, Dang, Cong Phi
, Bhunyakarnjanarat, Thansita
, Chantraprapawat, Bhumdhanin
in
Animals
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Disease Models, Animal
/ Endotoxemia - chemically induced
/ Endotoxemia - genetics
/ Endotoxemia - immunology
/ Enterocolitis - chemically induced
/ Enterocolitis - genetics
/ Enterocolitis - immunology
/ Female
/ Gene Deletion
/ Indomethacin - adverse effects
/ Lupus Erythematosus, Systemic - chemically induced
/ Lupus Erythematosus, Systemic - genetics
/ Lupus Erythematosus, Systemic - immunology
/ Macrophage Activation - drug effects
/ Macrophages - drug effects
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Receptors, IgG - genetics
/ Receptors, IgG - immunology
2021
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Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
Journal Article
Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut
2021
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Overview
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.
Publisher
MDPI
Subject
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Endotoxemia - chemically induced
/ Enterocolitis - chemically induced
/ Female
/ Indomethacin - adverse effects
/ Lupus Erythematosus, Systemic - chemically induced
/ Lupus Erythematosus, Systemic - genetics
/ Lupus Erythematosus, Systemic - immunology
/ Macrophage Activation - drug effects
/ Mice
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