Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts
| Autor: | Ning-Wei Zhu, Min Zhang, Fengyun Wang, Xiao-Lan Yin, Xu-Dong Tang, Lin Lv, Xiang-Xue Ma, Li-Ying Zhang, Bei-Huang Zhang, Haomeng Wu, Ting Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Inflammasomes Phytochemicals Chemical burn Pharmacology medicine.disease_cause Epithelium Bile Acids and Salts Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Esophagus Gastrointestinal Agents NLRP3 In vivo NLR Family Pyrin Domain-Containing 3 Protein medicine CaSR Animals Humans Secretion Medicine Chinese Traditional Cells Cultured Chemistry Inflammasome Tojapride Cell Biology Original Articles medicine.disease In vitro Rats oesophageal epithelium 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Irritants Molecular Medicine Original Article NLRP3 inflammasome activation Irritation Receptors Calcium-Sensing reflux oesophagitis medicine.drug |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine‐mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL‐1β and IL‐18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride‐pretreated SV40‐immortalized human oesophageal epithelial cells (HET‐1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway‐related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR‐mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up‐regulated the CaSR‐mediated NLRP3 inflammasome pathway and increased caspase‐1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR‐mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure. |
| Databáze: | OpenAIRE |
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