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Research
In vitro/vivo Mechanism of Action of S100A12 in Sepsis-induced ARDS
Ye Shen
People's Hospital of Hangzhou Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7328-1403
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective
Sepsis is a multiple organ dysfunction elicited by the dysregulated host immune response to microbial infection. Acute respiratory distress syndrome (ARDS) is a serious and acute inflammatory lung injury resulting from sepsis and other serious diseases. The present study aims to investigate the role of S100A12, a pro-inflammatory factor, in the pathophysiologic mechanism underlying the process in sepsis-induced ARDS.
Methods
The blood samples and clinical base line of study subjects were collected. C57BL/6 mice underwent cecal ligation and puncture (CLP) to establish sepsis models. Hematoxylin and Eosin (H&E) Staining was performed to observe pathological changes. Enzyme-Linked Immunosorbent Assay (ELISA) and specific commercial assay kits were employed to analyze the levels of inflammatory cytokines and antioxidant capacity, respectively. Western blot, immunohistochemistry (IHC) staining and reverse-transcriptase quantitative real-time PCR (RT-qPCR) were performed to determine target gene and protein expression. TUNEL Assay and Flow Cytometry were performed to assay cell apoptosis.
Results
The levels of S100A12 and sRAGE are upregulated in the serum of patients with Sepsis-induced ARDS and sepsis mice. Furthermore, higher cell apoptosis rate was observed in lung tissue of sepsis mice. In addition, S100A12 resulted in excessive mucins and the secretion of inflammatory cytokines secretion, and promoted the expression of chemokines and cell adhesion molecules via activating NLRP3 inflammasome pathway in NHBE cells. Finally, S100A12 increased oxidative stress status and cell apoptosis in NHBE cells.
Conclusion
The present study provides evidence that S100A12 is closely related to pathogenesis of sepsis-induced ARDS. Hence, S100A12 may be a useful biomarker of pulmonary injuries for clinical diagnosis of sepsis-induced ARDS.
Keywords
S100A12, sepsis, acute respiratory distress syndrome, inflammation, apoptosis
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This is a preprint. It has not completed peer review.
Research
In vitro/vivo Mechanism of Action of S100A12 in Sepsis-induced ARDS
Ye Shen
People's Hospital of Hangzhou Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7328-1403
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 13 Jan, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective
Sepsis is a multiple organ dysfunction elicited by the dysregulated host immune response to microbial infection. Acute respiratory distress syndrome (ARDS) is a serious and acute inflammatory lung injury resulting from sepsis and other serious diseases. The present study aims to investigate the role of S100A12, a pro-inflammatory factor, in the pathophysiologic mechanism underlying the process in sepsis-induced ARDS.
Methods
The blood samples and clinical base line of study subjects were collected. C57BL/6 mice underwent cecal ligation and puncture (CLP) to establish sepsis models. Hematoxylin and Eosin (H&E) Staining was performed to observe pathological changes. Enzyme-Linked Immunosorbent Assay (ELISA) and specific commercial assay kits were employed to analyze the levels of inflammatory cytokines and antioxidant capacity, respectively. Western blot, immunohistochemistry (IHC) staining and reverse-transcriptase quantitative real-time PCR (RT-qPCR) were performed to determine target gene and protein expression. TUNEL Assay and Flow Cytometry were performed to assay cell apoptosis.
Results
The levels of S100A12 and sRAGE are upregulated in the serum of patients with Sepsis-induced ARDS and sepsis mice. Furthermore, higher cell apoptosis rate was observed in lung tissue of sepsis mice. In addition, S100A12 resulted in excessive mucins and the secretion of inflammatory cytokines secretion, and promoted the expression of chemokines and cell adhesion molecules via activating NLRP3 inflammasome pathway in NHBE cells. Finally, S100A12 increased oxidative stress status and cell apoptosis in NHBE cells.
Conclusion
The present study provides evidence that S100A12 is closely related to pathogenesis of sepsis-induced ARDS. Hence, S100A12 may be a useful biomarker of pulmonary injuries for clinical diagnosis of sepsis-induced ARDS.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7