CD123 thioaptamer protects against sepsis via the blockade between IL-3/CD123 in a cecal ligation and puncture rat model

Abstract

Sepsis is one of the most common causes of death in ICU and especially is a harmful and a life-threatened disease to pediatrics in the world. It has been demonstrated that IL-3 plays an essential role in the processing of sepsis and the inhibition of IL-3 may alleviate sepsis progress. In our previous study, we selected a novel CD123 aptamer successfully which could inhibit the interaction of CD123 and IL-3. The aim of this study is to explore the protection ability of the first thioaptamer SS30 against sepsis in a cecal ligation and puncture (CLP) rat model. Serum IL-3 level of sepsis patients was assessed by ELISA. CLP rat model was applied in all experimental groups. CD123 thioaptamer SS30 and CD123 antibody were used to block the recognition between IL-3 and CD123. Body weight, temperature, blood gas, MAP, and serum cytokines of four grouped rats were assessed. Flow cytometry was utilized to evaluate JAK2 and STAT5 proteins. After the administration of SS30 or CD123 antibody, the rats in SS30 and CD123 antibody group had lower cytokines values(lactate, TNF-α, IL-1β, and IL-6), whereas exhibited higher value of core temperature, MAP, PO₂/FiO₂, and ETCO₂ than those in the CLP group. The expression level of phosphorylated JAK2 and STAT5 was declined and the survival rate of rats was increased. In addition, the protection ability of SS30 was better than CD123 antibody. Therefore, CD123 thioaptamer SS30 could reduce mortality by down-regulating the phosphorylated JAK2/STAT5 signaling pathway, and reduce serum cytokines which involving in sepsis development in CLP rat model.

Keywords:

• CD123 aptamer
• IL-3
• protection
• CLP
• sepsis

Acknowledgments

We would like to thank everyone who generously agreed to be interviewed for this research.

Declarations

 

Consent for publication

Written informed consent was obtained from the patient for the publication of this report and any accompanying images.

Availability of data and materials

All data concerning the case are presented in the manuscript.

Competing interests

The authors declare that they have no competing interests.

Authors’ contribution

This is a research article and all authors have read and approved the manuscript. Authors’ contribution: conceived and designed the experiments: L.Z. and J.Z.; Performed the experiments: J.Z., M.W., Y.Y., G.W., F.C., and Q.L.; Analyzed the data: L.Z.; Contributed reagents/materials/analysis tools: Y.Y., G.W., F.C., and Q.L.; Wrote the paper: L.Z.

Compliance with ethical standards

 

Disclosure statement

The authors declare that they have no conflict of interest.

Ethical approval

The protocol of the study using patient samples and the animal study in this paper was reviewed and approved by the Ethics Committee of Xi’an Jiaotong University Affiliated Children’s Hospital (Xi’an Children’s Hospital, Xi’an, China), No. C2018004.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Funding

This work was supported by the Xi’an Science Technology program [grant no. SF1510(4)] and Shaanxi Provincial Program [grant no. 2019SF-207]. The funder of these two programs Dr. Liyu Zhang participated in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.