Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide with inflammation and injury in airway epithelial cells. However, few treatment options effectively reduce severity. We previously found that Nur77 is involved in lipopolysaccharide-induced inflammation and injury of...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1200110/full |
| _version_ | 1827921981761126400 |
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| author | Chenli Chang Fengming He Mingtao Ao Jun Chen Tao Yu Weiyu Li Baicun Li Meijuan Fang Ting Yang |
| author_facet | Chenli Chang Fengming He Mingtao Ao Jun Chen Tao Yu Weiyu Li Baicun Li Meijuan Fang Ting Yang |
| author_sort | Chenli Chang |
| collection | DOAJ |
| description | Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide with inflammation and injury in airway epithelial cells. However, few treatment options effectively reduce severity. We previously found that Nur77 is involved in lipopolysaccharide-induced inflammation and injury of lung tissue. Here, we established an in vitro model of COPD-related inflammation and injury in 16-HBE cells induced by cigarette smoke extract (CSE). In these cells, Nur77 expression and localization to the endoplasmic reticulum (ER) increased following CSE treatment, as did ER stress marker (BIP, ATF4, CHOP) expression, inflammatory cytokine expression, and apoptosis. The flavonoid derivative, named B6, which was shown to be a modulator of Nur77 in previous screen, molecular dynamics simulation revealed that B6 binds strongly to Nur77 through hydrogen bonding and hydrophobic interactions. Treating CSE-stimulated 16-HBE cells with B6 resulted in a reduction of both inflammatory cytokine expression and secretion, as well as attenuated apoptosis. Furthermore, B6 treatment resulted in a decrease in Nur77 expression and translocation to the ER, which was accompanied by a concentration-dependent reduction in the expression of ER stress markers. Meanwhile, B6 played a similar role in CSE-treated BEAS-2B cells. These combined effects suggest that B6 could inhibit inflammation and apoptosis in airway epithelial cells after cigarette smoke stimulation, and support its further development as a candidate intervention for treating COPD-related airway inflammation. |
| first_indexed | 2024-03-13T04:35:32Z |
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| id | doaj.art-b4f090c65ab34cebb600a2c0dca8b767 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T04:35:32Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-b4f090c65ab34cebb600a2c0dca8b7672023-06-19T06:53:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.12001101200110Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cellsChenli Chang0Fengming He1Mingtao Ao2Jun Chen3Tao Yu4Weiyu Li5Baicun Li6Meijuan Fang7Ting Yang8China-Japan Friendship Hospital, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaCollege of Pharmacy, Hubei University of Science and Technology, Xianning, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaChina-Japan Friendship Hospital, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaChina-Japan Friendship Hospital, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaChina-Japan Friendship Hospital, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaChina-Japan Friendship Hospital, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaChronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide with inflammation and injury in airway epithelial cells. However, few treatment options effectively reduce severity. We previously found that Nur77 is involved in lipopolysaccharide-induced inflammation and injury of lung tissue. Here, we established an in vitro model of COPD-related inflammation and injury in 16-HBE cells induced by cigarette smoke extract (CSE). In these cells, Nur77 expression and localization to the endoplasmic reticulum (ER) increased following CSE treatment, as did ER stress marker (BIP, ATF4, CHOP) expression, inflammatory cytokine expression, and apoptosis. The flavonoid derivative, named B6, which was shown to be a modulator of Nur77 in previous screen, molecular dynamics simulation revealed that B6 binds strongly to Nur77 through hydrogen bonding and hydrophobic interactions. Treating CSE-stimulated 16-HBE cells with B6 resulted in a reduction of both inflammatory cytokine expression and secretion, as well as attenuated apoptosis. Furthermore, B6 treatment resulted in a decrease in Nur77 expression and translocation to the ER, which was accompanied by a concentration-dependent reduction in the expression of ER stress markers. Meanwhile, B6 played a similar role in CSE-treated BEAS-2B cells. These combined effects suggest that B6 could inhibit inflammation and apoptosis in airway epithelial cells after cigarette smoke stimulation, and support its further development as a candidate intervention for treating COPD-related airway inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2023.1200110/fullNur77airway epithelial cellsinflammationapoptosissmall molecule derivative of flavonoid |
| spellingShingle | Chenli Chang Fengming He Mingtao Ao Jun Chen Tao Yu Weiyu Li Baicun Li Meijuan Fang Ting Yang Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells Frontiers in Pharmacology Nur77 airway epithelial cells inflammation apoptosis small molecule derivative of flavonoid |
| title | Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells |
| title_full | Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells |
| title_fullStr | Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells |
| title_full_unstemmed | Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells |
| title_short | Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells |
| title_sort | inhibition of nur77 expression and translocation by compound b6 reduces er stress and alleviates cigarette smoke induced inflammation and injury in bronchial epithelial cells |
| topic | Nur77 airway epithelial cells inflammation apoptosis small molecule derivative of flavonoid |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1200110/full |
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