Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is a lethal gastrointestinal tract disease that occurs in premature infants. Adenosine receptor A2B (A2BR) regulates the inflammation cytokine secretion and immune cell infiltration in the colonic pathophysiology conditions. In the present study, we aim to determine t...
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/1562973 |
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| author | Lie Huang Juan Fan Yan-Xiang Chen Jian-Hui Wang |
| author_facet | Lie Huang Juan Fan Yan-Xiang Chen Jian-Hui Wang |
| author_sort | Lie Huang |
| collection | DOAJ |
| description | Necrotizing enterocolitis (NEC) is a lethal gastrointestinal tract disease that occurs in premature infants. Adenosine receptor A2B (A2BR) regulates the inflammation cytokine secretion and immune cell infiltration in the colonic pathophysiology conditions. In the present study, we aim to determine the roles of A2BR in the development of NEC. A NEC rat model was established and treated with A2BR agonist-BAY60-6583 or A2BR antagonist-PSB1115. Animals in the control group were free from any interventions. Our results showed that the inhibition of A2BR PSB1115 improved intestinal injury and inflammation in newborn NEC rats. The expression levels of caspase-3 and the ratio of apoptotic cells were upregulated in NEC rats, and these indices were downregulated after treating with PSB1115 but further upregulated by BAY60-6583. Meanwhile, a similar trend was also witnessed in the changes of MPO activities and proinflammatory cytokines including IL-6, IFN-γ, and TNF-α. However, the anti-inflammatory cytokine IL-10 in the NECP group was significantly higher than that in the NEC and NECB groups (p<0.05, respectively). Moreover, the expression of Ki67 was significantly increased in the NECP group as compared with those of the NEC and the NECB groups (p<0.05, respectively). Collectively, our study suggested that the inhibition of A2BR attenuates NEC in the neonatal rat, at least partially through the modulation of inflammation and the induction of epithelial cell proliferation. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2020-01-01 |
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| spelling | doaj-art-f16ffb1e10e14e948d59e6cd8e2e313a2025-02-03T01:05:21ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/15629731562973Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing EnterocolitisLie Huang0Juan Fan1Yan-Xiang Chen2Jian-Hui Wang3Department of Neonatology, The First People’s Hospital of Yinchuan, Yinchuan, Ningxia 750001, ChinaDepartment of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Neonatology, The First People’s Hospital of Yinchuan, Yinchuan, Ningxia 750001, ChinaDepartment of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaNecrotizing enterocolitis (NEC) is a lethal gastrointestinal tract disease that occurs in premature infants. Adenosine receptor A2B (A2BR) regulates the inflammation cytokine secretion and immune cell infiltration in the colonic pathophysiology conditions. In the present study, we aim to determine the roles of A2BR in the development of NEC. A NEC rat model was established and treated with A2BR agonist-BAY60-6583 or A2BR antagonist-PSB1115. Animals in the control group were free from any interventions. Our results showed that the inhibition of A2BR PSB1115 improved intestinal injury and inflammation in newborn NEC rats. The expression levels of caspase-3 and the ratio of apoptotic cells were upregulated in NEC rats, and these indices were downregulated after treating with PSB1115 but further upregulated by BAY60-6583. Meanwhile, a similar trend was also witnessed in the changes of MPO activities and proinflammatory cytokines including IL-6, IFN-γ, and TNF-α. However, the anti-inflammatory cytokine IL-10 in the NECP group was significantly higher than that in the NEC and NECB groups (p<0.05, respectively). Moreover, the expression of Ki67 was significantly increased in the NECP group as compared with those of the NEC and the NECB groups (p<0.05, respectively). Collectively, our study suggested that the inhibition of A2BR attenuates NEC in the neonatal rat, at least partially through the modulation of inflammation and the induction of epithelial cell proliferation.http://dx.doi.org/10.1155/2020/1562973 |
| spellingShingle | Lie Huang Juan Fan Yan-Xiang Chen Jian-Hui Wang Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis Mediators of Inflammation |
| title | Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis |
| title_full | Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis |
| title_fullStr | Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis |
| title_full_unstemmed | Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis |
| title_short | Inhibition of A2B Adenosine Receptor Attenuates Intestinal Injury in a Rat Model of Necrotizing Enterocolitis |
| title_sort | inhibition of a2b adenosine receptor attenuates intestinal injury in a rat model of necrotizing enterocolitis |
| url | http://dx.doi.org/10.1155/2020/1562973 |
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