The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes
ObjectiveOur previous clinical study showed that low lung levels of CC16 strongly influence the occurrence and development of ARDS. The aim of the present study was to evaluate the therapeutic effect of rCC16 on LPS-induced inflammation in A549 cells and to determine its mechanism.MethodsCell apopto...
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| Format: | Article |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.01060/full |
| _version_ | 1811222780258025472 |
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| author | Jinle Lin Jinle Lin Jiemei Li Min Shu Weigang Wu Wenwu Zhang Qingli Dou Jian Wu Xiaobin Zeng Xiaobin Zeng |
| author_facet | Jinle Lin Jinle Lin Jiemei Li Min Shu Weigang Wu Wenwu Zhang Qingli Dou Jian Wu Xiaobin Zeng Xiaobin Zeng |
| author_sort | Jinle Lin |
| collection | DOAJ |
| description | ObjectiveOur previous clinical study showed that low lung levels of CC16 strongly influence the occurrence and development of ARDS. The aim of the present study was to evaluate the therapeutic effect of rCC16 on LPS-induced inflammation in A549 cells and to determine its mechanism.MethodsCell apoptosis and inflammation was induced by LPS stimulation. The cytotoxic effect of rCC16 was evaluated using the MTT assay. Cytokine levels were determined using enzyme-linked immunosorbent assays. The molecular mechanism of rCC16 was investigated by analyzing relevant signaling pathways.ResultsThe LPS treatment of A549 cells significantly decreased cell viability, increased the levels of the apoptotic proteins Bax, Bak and Cleaved Caspase-3, the secretion of inflammatory cytokines, and the expression levels of TLR4, p-NF/κB, MAPK proteins. While the levels of Bcl-2, p-AKT, p-mTOR, p-ERK1/2, NF/κB, p-AMPK, and p-p38 were significantly decreased in LPS-treated A549 cells. Our experimental results also confirmed that rCC16 inhibited LPS-induced apoptosis, promoted A549 cell proliferation by activating the PI3K/AKT/mTOR/ERK1/2 pathway, and inhibited the release of certain inflammatory factors, especially HMGB1, through dephosphorylation and inactivation of the TLR4/NF-κB/AMPK signaling pathways.ConclusionThese results highlight the potential utility of CC16 as an important cytokine for the prevention or treatment of inflammation and show that CC16 may play an important role in the future clinical treatment of ARDS. |
| first_indexed | 2024-04-12T08:21:14Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T08:21:14Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-a235f5cf8e194ecaae87493d54c519ad2022-12-22T03:40:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-07-011110.3389/fphar.2020.01060552874The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung PneumocytesJinle Lin0Jinle Lin1Jiemei Li2Min Shu3Weigang Wu4Wenwu Zhang5Qingli Dou6Jian Wu7Xiaobin Zeng8Xiaobin Zeng9Department of Emergency Medicine, Shenzhen Baoan First People’s Hospital, Nanfang Medical University, Shenzhen, ChinaDepartment of Respiratory and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaCenter Laboratory of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, ChinaEmergency Department, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, ChinaCenter Laboratory of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, ChinaDepartment of Emergency Medicine, Shenzhen Baoan First People’s Hospital, Nanfang Medical University, Shenzhen, ChinaDepartment of Emergency Medicine, Shenzhen Baoan First People’s Hospital, Nanfang Medical University, Shenzhen, ChinaDepartment of Respiratory and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaCenter Laboratory of Longhua Branch and Department of Infectious Disease, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, ChinaGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Medicine School of Shenzhen University, Shenzhen, ChinaObjectiveOur previous clinical study showed that low lung levels of CC16 strongly influence the occurrence and development of ARDS. The aim of the present study was to evaluate the therapeutic effect of rCC16 on LPS-induced inflammation in A549 cells and to determine its mechanism.MethodsCell apoptosis and inflammation was induced by LPS stimulation. The cytotoxic effect of rCC16 was evaluated using the MTT assay. Cytokine levels were determined using enzyme-linked immunosorbent assays. The molecular mechanism of rCC16 was investigated by analyzing relevant signaling pathways.ResultsThe LPS treatment of A549 cells significantly decreased cell viability, increased the levels of the apoptotic proteins Bax, Bak and Cleaved Caspase-3, the secretion of inflammatory cytokines, and the expression levels of TLR4, p-NF/κB, MAPK proteins. While the levels of Bcl-2, p-AKT, p-mTOR, p-ERK1/2, NF/κB, p-AMPK, and p-p38 were significantly decreased in LPS-treated A549 cells. Our experimental results also confirmed that rCC16 inhibited LPS-induced apoptosis, promoted A549 cell proliferation by activating the PI3K/AKT/mTOR/ERK1/2 pathway, and inhibited the release of certain inflammatory factors, especially HMGB1, through dephosphorylation and inactivation of the TLR4/NF-κB/AMPK signaling pathways.ConclusionThese results highlight the potential utility of CC16 as an important cytokine for the prevention or treatment of inflammation and show that CC16 may play an important role in the future clinical treatment of ARDS.https://www.frontiersin.org/article/10.3389/fphar.2020.01060/fullCC16Acute Respiratory Distress SyndromeLPSinflammationapoptosis |
| spellingShingle | Jinle Lin Jinle Lin Jiemei Li Min Shu Weigang Wu Wenwu Zhang Qingli Dou Jian Wu Xiaobin Zeng Xiaobin Zeng The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes Frontiers in Pharmacology CC16 Acute Respiratory Distress Syndrome LPS inflammation apoptosis |
| title | The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes |
| title_full | The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes |
| title_fullStr | The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes |
| title_full_unstemmed | The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes |
| title_short | The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes |
| title_sort | rcc16 protein protects against lps induced cell apoptosis and inflammatory responses in human lung pneumocytes |
| topic | CC16 Acute Respiratory Distress Syndrome LPS inflammation apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.01060/full |
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