Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice
The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in n...
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2021-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2021/1180543 |
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author | Julie Chi Chow Hsiu-Chu Chou Jaulang Hwang Chung-Ming Chen |
author_facet | Julie Chi Chow Hsiu-Chu Chou Jaulang Hwang Chung-Ming Chen |
author_sort | Julie Chi Chow |
collection | DOAJ |
description | The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical. This study is aimed at determining whether anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week. On postnatal days 2, 4, and 6, the mice were injected intraperitoneally with PBS alone or with anti-Tn monoclonal antibodies at 25 μg/g body weight in 50 μL phosphate-buffered saline (PBS). The mice were divided into four study groups: RA + PBS, RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The kidneys were excised for histology, oxidative stress, cytokine, and Western blot analyses on postnatal day 7. The O2 + PBS mice exhibited significantly higher kidney injury scores, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and nuclear factor-κB (NF-κB) expression, and cytokine levels than did the RA + PBS mice or RA + anti-Tn mice. Anti-Tn monoclonal antibody treatment reduced kidney injury and cytokine levels to normoxic levels. The attenuation of kidney injury was accompanied by a reduction of oxidative stress and NF-κB expression. Therefore, we propose that anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice. |
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institution | Kabale University |
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language | English |
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series | Mediators of Inflammation |
spelling | doaj-art-122f2928708e486883efdf75188560e42025-02-03T07:23:56ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/11805431180543Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal MiceJulie Chi Chow0Hsiu-Chu Chou1Jaulang Hwang2Chung-Ming Chen3Department of Pediatrics, Chi Mei Medical Center, Tainan, TaiwanDepartment of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanTaipei Cancer Center, Taipei Medical University, Taipei, TaiwanDepartment of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanThe Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical. This study is aimed at determining whether anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week. On postnatal days 2, 4, and 6, the mice were injected intraperitoneally with PBS alone or with anti-Tn monoclonal antibodies at 25 μg/g body weight in 50 μL phosphate-buffered saline (PBS). The mice were divided into four study groups: RA + PBS, RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The kidneys were excised for histology, oxidative stress, cytokine, and Western blot analyses on postnatal day 7. The O2 + PBS mice exhibited significantly higher kidney injury scores, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and nuclear factor-κB (NF-κB) expression, and cytokine levels than did the RA + PBS mice or RA + anti-Tn mice. Anti-Tn monoclonal antibody treatment reduced kidney injury and cytokine levels to normoxic levels. The attenuation of kidney injury was accompanied by a reduction of oxidative stress and NF-κB expression. Therefore, we propose that anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice.http://dx.doi.org/10.1155/2021/1180543 |
spellingShingle | Julie Chi Chow Hsiu-Chu Chou Jaulang Hwang Chung-Ming Chen Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice Mediators of Inflammation |
title | Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice |
title_full | Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice |
title_fullStr | Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice |
title_full_unstemmed | Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice |
title_short | Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice |
title_sort | anti tn monoclonal antibody ameliorates hyperoxia induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice |
url | http://dx.doi.org/10.1155/2021/1180543 |
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