Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway
Abstract Sepsis is a systemic inflammatory response syndrome attributed to infection, while sepsis‐induced acute lung injury (ALI) has high morbidity and mortality. Here, we aimed to explore the specific mechanism of hypaphorine's anti‐inflammatory effects in ALI. Lipopolysaccharide (LPS) was a...
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| Format: | Article |
| Language: | English |
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Wiley
2021-10-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12418 |
| _version_ | 1818726967105552384 |
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| author | Yu‐Hua Ding Run‐Xin Miao Qiang Zhang |
| author_facet | Yu‐Hua Ding Run‐Xin Miao Qiang Zhang |
| author_sort | Yu‐Hua Ding |
| collection | DOAJ |
| description | Abstract Sepsis is a systemic inflammatory response syndrome attributed to infection, while sepsis‐induced acute lung injury (ALI) has high morbidity and mortality. Here, we aimed to explore the specific mechanism of hypaphorine's anti‐inflammatory effects in ALI. Lipopolysaccharide (LPS) was adopted to construct ALI model both in vivo and in vitro. BEAS‐2B cell viability and apoptosis was testified by the MTT assay and flow cytometry. Reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were performed to examine the expression of proinflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IL‐18), and Western blot was adopted to examine the expression of the apoptosis‐related proteins (Bax, Bcl2, and Caspase3) and the DUSP1/p38/JNK signaling pathway. At the same time, lung injury score, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were monitored. The dry/wet weight method was used to examine lung edema, and the total protein content in BALF was determined to test pulmonary vascular permeability. As the data suggested, hypaphorine inhibited the LPS‐mediated apoptosis of alveolar epithelial cells. What is more, hypaphorine attenuated the expression of inflammatory factors (IL‐1β, IL‐6, TNF‐α, and IL‐18) and inactivated the p38/JNK signaling pathway through upregulating DUSP1 in a dose‐dependent manner. Meanwhile, DUSP1 knockdown weakened the anti‐inflammatory effect of hypaphorine on LPS‐mediated lung injury. Furthermore, hypaphorine also relieved LPS induced ALI in rats with anti‐inflammatory effects. Taken together, hypaphorine prevented LPS‐mediated ALI and proinflammatory response via inactivating the p38/JNK signaling pathway by upregulating DUSP1. |
| first_indexed | 2024-12-17T22:06:37Z |
| format | Article |
| id | doaj.art-301b58d5738741ccb5acc1fbefdd1355 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-17T22:06:37Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-301b58d5738741ccb5acc1fbefdd13552022-12-21T21:30:50ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502021-10-01371088389310.1002/kjm2.12418Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathwayYu‐Hua Ding0Run‐Xin Miao1Qiang Zhang2Department of Pharmacy Zaozhuang Hospital of Traditional Chinese Medicine Zaozhuang Shandong ChinaDepartment of Emergency Zaozhuang Hospital of Traditional Chinese Medicine Zaozhuang Shandong ChinaDepartment of Pharmacy Zaozhuang Hospital of Traditional Chinese Medicine Zaozhuang Shandong ChinaAbstract Sepsis is a systemic inflammatory response syndrome attributed to infection, while sepsis‐induced acute lung injury (ALI) has high morbidity and mortality. Here, we aimed to explore the specific mechanism of hypaphorine's anti‐inflammatory effects in ALI. Lipopolysaccharide (LPS) was adopted to construct ALI model both in vivo and in vitro. BEAS‐2B cell viability and apoptosis was testified by the MTT assay and flow cytometry. Reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were performed to examine the expression of proinflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IL‐18), and Western blot was adopted to examine the expression of the apoptosis‐related proteins (Bax, Bcl2, and Caspase3) and the DUSP1/p38/JNK signaling pathway. At the same time, lung injury score, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were monitored. The dry/wet weight method was used to examine lung edema, and the total protein content in BALF was determined to test pulmonary vascular permeability. As the data suggested, hypaphorine inhibited the LPS‐mediated apoptosis of alveolar epithelial cells. What is more, hypaphorine attenuated the expression of inflammatory factors (IL‐1β, IL‐6, TNF‐α, and IL‐18) and inactivated the p38/JNK signaling pathway through upregulating DUSP1 in a dose‐dependent manner. Meanwhile, DUSP1 knockdown weakened the anti‐inflammatory effect of hypaphorine on LPS‐mediated lung injury. Furthermore, hypaphorine also relieved LPS induced ALI in rats with anti‐inflammatory effects. Taken together, hypaphorine prevented LPS‐mediated ALI and proinflammatory response via inactivating the p38/JNK signaling pathway by upregulating DUSP1.https://doi.org/10.1002/kjm2.12418acute lung injurydual‐specific phosphatase 1hypaphorineinflammationsepsis |
| spellingShingle | Yu‐Hua Ding Run‐Xin Miao Qiang Zhang Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway Kaohsiung Journal of Medical Sciences acute lung injury dual‐specific phosphatase 1 hypaphorine inflammation sepsis |
| title | Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway |
| title_full | Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway |
| title_fullStr | Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway |
| title_full_unstemmed | Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway |
| title_short | Hypaphorine exerts anti‐inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway |
| title_sort | hypaphorine exerts anti inflammatory effects in sepsis induced acute lung injury via modulating dusp1 p38 jnk pathway |
| topic | acute lung injury dual‐specific phosphatase 1 hypaphorine inflammation sepsis |
| url | https://doi.org/10.1002/kjm2.12418 |
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