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

Lin, Jinle; Li, Jiemei; Shu, Min; Wu, Wentao; Zhang, Wenwu; Dou, Qingli; Wu, Jiahui; Zeng, Xiaobin

doi:10.3389/fphar.2020.01060

Cited by 16 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pang et al also showed that 5 µg/mL rCC16 inhibits the expressions of TNF-α, IL-6, and IL-8 in LPS-treated RAW264.7 cells via NF-κB and p38 MAPK pathways [ 31 ]. In lung epithelial cells, a recent study found that rCC16 protects against LPS-induced apoptosis and inflammatory responses in A549 cells [ 49 ]. However, rCC16 was provided in supraphysiological concentrations, which range from 50 to 200 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection

Almuntashiri

Han

Zhu

et al. 2021

IJMS

View full text Add to dashboard Cite

Gram-negative (G-) bacteria are the leading cause of hospital-acquired pneumonia in the United States. The devastating damage caused by G- bacteria results from the imbalance of bactericidal effects and overwhelming inflammation. Despite decades of research, the underlying mechanisms by which runaway inflammation is developed remain incompletely understood. Clara Cell Protein 16 (CC16), also known as uteroglobin, is the major protein secreted by Clara cells and the most abundant protein in bronchoalveolar lavage fluid (BALF). However, the regulation and functions of CC16 during G- bacterial infection are unknown. In this study, we aimed to assess the regulation of CC16 in response to Klebsiella pneumoniae (K. pneu) and to investigate the role of CC16 in bronchial epithelial cells. After K. pneu infection, we found that CC16 mRNA expression was significantly decreased in bronchial epithelial cells. Our data also showed that K. pneu infection upregulated cytokine and chemokine genes, including IL-1β, IL-6, and IL-8 in BEAS-2B cells. Endogenously overexpressed CC16 in BEAS-2B cells provided an anti-inflammatory effect by reducing these markers. We also observed that endogenous CC16 can repress NF-κB reporter activity. In contrast, the recombinant CC16 (rCC16) did not show an anti-inflammatory effect in K. pneu-infected cells or suppression of NF-κB promoter activity. Moreover, the overexpression of CC16 reduced reactive oxygen species (ROS) levels and protected BEAS-2B cells from K. pneu-induced apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection

Almuntashiri

Han

Zhu

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…We also found that there are physiological interrelations between some of the investigated biomarkers and traditional indicators. Evidence from our previous research 19 and other 20,21 suggests that CC16 positively correlates with Scr, Lac and NT-proBNP. This might related to the anti-inflammatory function, immune system activation, and lactate metabolism pathway related to prephosphorylation.…”

Section: Discussionmentioning

confidence: 67%

Enhancing-ARDS diagnostics for ICU patients: a retrospective, nested case-control study to develop a biomarker-based model

Fu¹,

Lin²,

Seery³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: To investigate whether a series of biomarkers including club cell protein 16 (CC16), angiopoietin 2(Ang-2), soluble receptor for advanced glycation end-products (sRAGE), high-mobility group box 1 protein (HMGB1), and surfactant protein D (SPD) could be utilized for identifying patients, thereby increasing the diagnostic value of acute respiratory distress syndrome(ARDS) in intensive care unit (ICU). Methods: 211 ICU admissions were enrolled in this retrospective, nested case-control study. These patients were then divided into ARDS (n=79) and non-ARDS (n=132) groups according to the Berlin criteria on ICU day 1. Patient characteristics, vital signs, and laboratory examinations were collected within three hours of admission. Five inflammatory associated plasma biomarkers, as well as lung epithelial and endothelial injury which included CC16, Ang-2, sRAGE, HMGB1 and SPD were measured in the morning of day two in the ICU. Diagnostic values were analyzed with receiver operating characteristic (ROC) curves. Pearson’s product-moment correlation coefficient and multivariate logistic regression analysis were applied for predictive purposes. Results: C-reactive protein (CRP), NT-proBNP, and PH values for traditional indicators and five biomarkers were analyzed with an objective ARDS indicator, the PaO2/FiO2 ratio. Evidence suggests that only four of potential indicators analyzed here, and CRP hold high diagnostic value. The area under curve (AUC) for each were as follows: CC16 (AUC: 0.752; 95%CI0.680-0.824), Ang-2 (AUC: 0.695; 95%CI 0.620 -0.770), HMGB1 (AUC: 0.668; 95%CI 0.592-0.744), sRAGE (AUC: 0.665; 95%CI 0.588-0.743), CRP (AUC: 0.701; 95%CI 0.627-0.776). No single indicator surpassed the diagnostic capability of the PaO2/FiO2 ratio which had an AUC: 0.844(95%CI 0.789-0.898), especially in terms of sensitivity. However, when the binary logistic model was transformed and the model was built, the AUC increased from 0.647(95%CI 0.568-0.726) to 0.911(95%CI 0.864-0.946). Among the combinations tested, PaO2/FiO2+CRP+Ang-2+CC16+HMGB1 resulted in an AUC of 0.910 (95%CI 0.863-0.945), while PaO2/FiO2+CRP+Ang-2+CC16+HMGB1+sRAGE+SPD have an AUC of 0.911(95%CI 0.864-0.946). Conclusions: A combination of the assessed biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we would recommend PaO2/FiO2+CRP+Ang-2+CC16+HMGB1 for clinical practice. This is because of the cost implications in contrast with the benefit involved in utilizing the more elaborate model. Although, further health economics research is required to consider this opportunity cost for emergency care policy.

show abstract

“…The PI3K/Akt signaling pathway regulates the release of inflammatory transmitters in inflammatory response in the lungs and airways (49). The latest studies demonstrated that during the SARS-CoV-2 infection, the PI3K/Akt/ mTOR pathway was activated in a dose-dependent manner which activated cell apoptosis process (50).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking analysis reveals the mechanism of asiaticoside on COVID-19

Huang¹,

Zhou²,

Gong³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Asiaticoside (AS) is a saponin extracted from the traditional Chinese herbal medicine Centella Asiatica, which has the effects of reducing inflammatory infiltration and anti-oxidation in pneumonia and combating pulmonary fibrosis. We hypothesize that AS might have therapeutic potential for the treatment of the coronavirus disease 2019 . With the help of network pharmacology and molecular docking techniques, this study discussed the underlying molecular mechanism of AS in the treatment of COVID-19. Methods:The molecular structure of AS was obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) system. The targets of AS were achieved using PharmMapper, SwissTargetPrediction, and the Comparative Toxicogenomics Database (CTD). The targets corresponding to COVID-19 were obtained using GeneCards, Online Mendelian Inheritance in Man (OMIM), and CTD database. Then, a target protein-protein interaction (PPI) network was formed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. A network of AS, COVID-19, and their co-targets was built using Cytoscape. Afterwards, the co-targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.Moreover, the predictions of crucial targets were further investigated by performing molecular docking with AS.Results: A total of 45 core targets of AS were found to be engaged in the pathogenesis of COVID-19. The KEGG enrichment analysis indicated that AS might be protective against COVID-19 through inflammationand immune-related signaling pathways, including interleukin-17 (IL-17) signaling, T helper 17 (Th17) cell differentiation pathway, Coronavirus disease-COVID-19, MAPK, the PI3K-Akt signaling pathway, and so on. The results of molecular docking showed that AS had a high affinity with those core targets. Conclusions:The beneficial effect of AS on COVID-19 might be through regulating multiple immune or inflammation-related targets and signaling pathways.

show abstract

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

Cited by 16 publications

References 37 publications

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection

Enhancing-ARDS diagnostics for ICU patients: a retrospective, nested case-control study to develop a biomarker-based model

Network pharmacology and molecular docking analysis reveals the mechanism of asiaticoside on COVID-19

Contact Info

Product

Resources

About