The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes

Lin，Jinle1,2; Li，Jiemei3; Shu，Min4; Wu，Weigang3; Zhang，Wenwu1; Dou，Qingli1; Wu，Jian2; Zeng，Xiaobin3,5

2020-07-14

10.3389/fphar.2020.01060

Frontiers in Pharmacology   影响因子和分区

1663-9812

1663-9812

Objective: Our 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. Methods: Cell 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. Results: The 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. Conclusion: These 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.

Acute Respiratory Distress Syndrome apoptosis CC16 inflammation LPS

SCI

英语

通讯

Natural Science Foundation of China[81503221] ; Science and Technology Planning Project of Shenzhen Municipality[JCYJ20180305123707368][JCYJ20180302144713444] ; Na t u r a l Science Foundation of Guangdong Province[2017A030313659]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000556342700001

FRONTIERS MEDIA SA

2-s2.0-85088793258

Scopus

1.Department of Emergency Medicine,Shenzhen Baoan First People’s Hospital,Nanfang Medical University,Shenzhen,China
2.Department of Respiratory and Critical Care Medicine,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Science,Guangzhou,China
3.Center 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,China
4.Emergency Department,Huazhong University of Science and Technology Union Shenzhen Hospital,Shenzhen,China
5.Guangdong Provincial Key Laboratory of Regional Immunity and Diseases,Medicine School of Shenzhen University,Shenzhen,China

Lin，Jinle,Li，Jiemei,Shu，Min,et al. The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes[J]. Frontiers in Pharmacology,2020,11.

Lin，Jinle.,Li，Jiemei.,Shu，Min.,Wu，Weigang.,Zhang，Wenwu.,...&Zeng，Xiaobin.(2020).The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes.Frontiers in Pharmacology,11.

Lin，Jinle,et al."The rCC16 Protein Protects Against LPS-Induced Cell Apoptosis and Inflammatory Responses in Human Lung Pneumocytes".Frontiers in Pharmacology 11(2020).