Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress

doi:10.21037/atm-21-6497

科研成果详情

题名	Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress
作者	Chen, Yang1; Lin, Pengcheng1; Nan, Wengang1; Su, Shanshan1; Zheng, Hong2; Gao, Hongchang2; Zhang, Dan1; Li, Yuping1
发表日期	2022-02
发表期刊	ANNALS OF TRANSLATIONAL MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Protein kinase C alpha (PKC alpha) acute lung injury (ALI) hyperinflammatory response oxidative stress NF-kappa B pathway
摘要	Background: The currently available treatment methods are ineffective in reducing mortality or improving outcomes in acute lung injury (ALI). The activation of protein kinase C alpha (PKC alpha) has recently been implicated in ALI development. We explored the potential therapeutic outcomes of PKC alpha inhibition in cases of ALI and to elucidate the related mechanisms. Methods: Indexes of lung inflammation and injury were examined in lipopolysaccharide (LPS)-treated C57BL/6J mice (male) and macrophages after pretreatment with a PKC alpha inhibitor. Tissues were collected to assess lung injury by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage fluid was used to measure the pulmonary edema, hyperinflammatory response, and oxidative stress by bicinchoninic acid (BCA) method and enzyme-linked immunosorbent assay (ELISA). We tested the effect of PKC alpha inhibition on LPS-induced proliferation, cytotoxicity, oxidative damage, and the release of inflammatory cytokines in macrophages using the Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) cytotoxicity assay kit, flow cytometry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and ELISA. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling pathway related proteins were detected by Western blot, immunohistochemistry (IHC), and immunofluorescence staining. Results: We observed that LPS upregulated PKC alpha phosphorylation, induced a hyperinflammatory response, and caused lung injury. However, PKC alpha inhibition effectively attenuated the changes caused by LPS. Moreover, we confirmed that inhibiting PKC alpha weakened the activity of the NF-kappa B pathway under LPS-induced ALI. These findings indicated that inhibition of PKC alpha is protective against LPS-induced hyperinflammatory response in ALI, this effect is likely to attributed to the downregulation of NF-kappa B signaling pathways. Conclusions: The results showed that PKC alpha inhibition could attenuate ALI which may closely related to its anti-inflammatory and anti-oxidative effects.
资助项目	Project of National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81970066, 81800075]
出版者	AME PUBL CO
出版地	SHATIN
ISSN	2305-5839
EISSN	2305-5847
卷号	10 期号:3 页码:132
DOI	10.21037/atm-21-6497
页数	14
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:000758732100011
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	35284551
PMC记录号	PMC8904993
通讯作者地址	[Li, Yuping]Wenzhou Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Peoples R China.
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/1163
专题	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科附属第二医院_核磁共振室
通讯作者	Li, Yuping
作者单位	1.Wenzhou Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Peoples R China; 2.Wenzhou Med Univ, Sch Pharmaceut Sci, Inst Metabon & Med NMR, Wenzhou, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
推荐引用方式 GB/T 7714	Chen, Yang,Lin, Pengcheng,Nan, Wengang,et al. Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress[J]. ANNALS OF TRANSLATIONAL MEDICINE,2022,10(3):132.
APA	Chen, Yang., Lin, Pengcheng., Nan, Wengang., Su, Shanshan., Zheng, Hong., ... & Li, Yuping. (2022). Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress. ANNALS OF TRANSLATIONAL MEDICINE, 10(3), 132.
MLA	Chen, Yang,et al."Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress".ANNALS OF TRANSLATIONAL MEDICINE 10.3(2022):132.