Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma
Increasing epidemiological evidence has proved that early-life exposure to inorganic arsenic (As) elevates the risks of childhood asthma. The present research aimed to explore susceptibility of respiratory As exposure to allergic asthma in a mouse model. BALB/c mice on postnatal day (PND) 28 were ex...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325001009 |
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| author | Xue Lu Zhu-Xia Tan Ya-Xin Yao Ze-Yan Li Yan-Yan Zhu Qian-Qun Yang Zhao Li Kun Peng Yan Wang De-Xiang Xu |
| author_facet | Xue Lu Zhu-Xia Tan Ya-Xin Yao Ze-Yan Li Yan-Yan Zhu Qian-Qun Yang Zhao Li Kun Peng Yan Wang De-Xiang Xu |
| author_sort | Xue Lu |
| collection | DOAJ |
| description | Increasing epidemiological evidence has proved that early-life exposure to inorganic arsenic (As) elevates the risks of childhood asthma. The present research aimed to explore susceptibility of respiratory As exposure to allergic asthma in a mouse model. BALB/c mice on postnatal day (PND) 28 were exposed to ddH2O or NaAsO2 aerosol for 4 hours daily over 5 consecutive weeks via respiratory tract. Mice were sensitized by intraperitoneal injection of ovalbumin (OVA) combined with Alum Adjuvant on PND42 and PND56. Subsequently, mice were challenged with ddH2O or 1 %OVA through a nebulizer for 3 days starting from PND63. In As-exposed mice, OVA-sensitized goblet cell hyperplasia and airway mucosal secretion did not worsen. OVA-induced inflammatory cell infiltration and upregulation of Th2 cytokines, including IL-4, IL-5, and IL-13, were not aggravated in As-exposed mice. Interestingly, airway hyperreactivity was intensified in As-exposed asthmatic mice. Mechanistically, OVA-induced elevation of 5-hydroxytryptamine (5-HT), probably secreted by pulmonary neuroendocrine cells (PNECs), was exacerbated in As-exposed mice. OVA-induced upregulation of tryptophan hydroxylase (TPH)1 and TPH2, two 5-HT synthases, was aggravated in As-exposed mouse lungs. LX1032, a specific TPH inhibitor, suppressed As-induced elevation of pulmonary 5-HT content in asthmatic mice. Moreover, LX1032 alleviated As-evoked airway hyperreactivity in asthmatic mice. These results suggest that respiratory As exposure elevates airway hyperreactivity partially through upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma, which provides significant insight about the hazards of environmental As exposure. |
| format | Article |
| id | doaj-art-19c6143fbb1343ae996609eba8ff2c45 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-19c6143fbb1343ae996609eba8ff2c452025-02-12T05:30:16ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117764Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthmaXue Lu0Zhu-Xia Tan1Ya-Xin Yao2Ze-Yan Li3Yan-Yan Zhu4Qian-Qun Yang5Zhao Li6Kun Peng7Yan Wang8De-Xiang Xu9Department of Toxicology, Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital, Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital, Anhui Medical University, Hefei, ChinaDepartment of Toxicology, Anhui Medical University, Hefei, ChinaDepartment of Toxicology, Anhui Medical University, Hefei, ChinaDepartment of Toxicology, Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital, Anhui Medical University, Hefei, ChinaThe Second Affiliated Hospital, Anhui Medical University, Hefei, ChinaDepartment of Toxicology, Anhui Medical University, Hefei, ChinaDepartment of Toxicology, Anhui Medical University, Hefei, China; Correspondence to: Department of Toxicology, Anhui Medical University, Hefei 230032, China.Increasing epidemiological evidence has proved that early-life exposure to inorganic arsenic (As) elevates the risks of childhood asthma. The present research aimed to explore susceptibility of respiratory As exposure to allergic asthma in a mouse model. BALB/c mice on postnatal day (PND) 28 were exposed to ddH2O or NaAsO2 aerosol for 4 hours daily over 5 consecutive weeks via respiratory tract. Mice were sensitized by intraperitoneal injection of ovalbumin (OVA) combined with Alum Adjuvant on PND42 and PND56. Subsequently, mice were challenged with ddH2O or 1 %OVA through a nebulizer for 3 days starting from PND63. In As-exposed mice, OVA-sensitized goblet cell hyperplasia and airway mucosal secretion did not worsen. OVA-induced inflammatory cell infiltration and upregulation of Th2 cytokines, including IL-4, IL-5, and IL-13, were not aggravated in As-exposed mice. Interestingly, airway hyperreactivity was intensified in As-exposed asthmatic mice. Mechanistically, OVA-induced elevation of 5-hydroxytryptamine (5-HT), probably secreted by pulmonary neuroendocrine cells (PNECs), was exacerbated in As-exposed mice. OVA-induced upregulation of tryptophan hydroxylase (TPH)1 and TPH2, two 5-HT synthases, was aggravated in As-exposed mouse lungs. LX1032, a specific TPH inhibitor, suppressed As-induced elevation of pulmonary 5-HT content in asthmatic mice. Moreover, LX1032 alleviated As-evoked airway hyperreactivity in asthmatic mice. These results suggest that respiratory As exposure elevates airway hyperreactivity partially through upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma, which provides significant insight about the hazards of environmental As exposure.http://www.sciencedirect.com/science/article/pii/S0147651325001009ArsenicRespiratory tractAllergic asthmaAirway hyperreactivityPulmonary neuroendocrine cell5-hydroxytryptamine |
| spellingShingle | Xue Lu Zhu-Xia Tan Ya-Xin Yao Ze-Yan Li Yan-Yan Zhu Qian-Qun Yang Zhao Li Kun Peng Yan Wang De-Xiang Xu Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma Ecotoxicology and Environmental Safety Arsenic Respiratory tract Allergic asthma Airway hyperreactivity Pulmonary neuroendocrine cell 5-hydroxytryptamine |
| title | Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma |
| title_full | Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma |
| title_fullStr | Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma |
| title_full_unstemmed | Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma |
| title_short | Inhaling arsenic aggravates airway hyperreactivity by upregulating PNEC-sourced 5-HT in OVA-induced allergic asthma |
| title_sort | inhaling arsenic aggravates airway hyperreactivity by upregulating pnec sourced 5 ht in ova induced allergic asthma |
| topic | Arsenic Respiratory tract Allergic asthma Airway hyperreactivity Pulmonary neuroendocrine cell 5-hydroxytryptamine |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325001009 |
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