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Application of innate immune activation peptide

An innate immunity and krait antibacterial peptide technology, applied in the field of biomedicine, can solve problems such as the loss of efficacy of antibiotic treatment, insufficient research and development of new anti-drug-resistant bacteria antibiotics, etc., to achieve enhanced antibacterial innate immune response, easy chemical synthesis and protein expression , the effect of small molecular weight

Inactive Publication Date: 2019-03-01
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Antibiotic therapy has lost its efficacy in many cases due to the emergence of methicillin-resistant S. aureus (MRSA) and insufficient development of new antibiotics against resistant bacteria

Method used

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  • Application of innate immune activation peptide
  • Application of innate immune activation peptide
  • Application of innate immune activation peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Pre-injection of cathelicidin-BF can effectively enhance the resistance of mice to S.aureus infection:

[0029]Experimental Animals SPF-grade C57BL / 6 mice, 6-8 weeks old, weighing 18-20 g, female, were purchased from Shanghai Slack Animal Co., Ltd. [SCXK (Shanghai) 2012-0002]. Mice were randomly marked and caged in the SPF animal room of Soochow University. Staphylococcus aureus S.aureus (ATCC25923) and clinically isolated methicillin-resistant Staphylococcus aureus (methicillin-resistant S.aureus, MRSA) were preserved in our laboratory. Cathelicidin-BF polypeptide, human cathelicidin antimicrobial peptide LL-37 (synthesized by Shanghai Gil Biochemical Company). Experimental animals and grouping C57BL / 6 mice were randomly divided into two groups, 5 in each group, the control group was solvent (PBS) injection group; the experimental group was cathelicidin-BF injection group (10mg / kg). 24h (-24h), 8h (-8h) and 4h (-4h) before bacterial infection, respectively, intraperi...

Embodiment 2

[0032] Intraperitoneal injection of cathelicidin-BF can promote chemotactic migration of neutrophils and monocytes / macrophages to the local peritoneal cavity:

[0033] The neutrophils and monocytes / macrophages infiltrated in the early stage of bacterial infection are important phagocytic and bactericidal cells, which play a vital role in eliminating pathogenic bacteria. In order to clarify whether cathelicidin-BF can enhance the peritoneal infiltration of phagocytes and promote the clearance of S.aureus, cells in the peritoneal fluid were collected 4h and 8h after intraperitoneal injection of cathelicidin-BF in mice for flow cytometric analysis. Peritoneal cells (1×10 6 ) was resuspended in an EP tube, washed once with PBS, resuspended in 100 μL of PBS, added cell surface marker antibodies (anti-mCD45, anti-mCD11B, anti-mLy6G, anti-mLy6C, anti-mF4 / 80), and kept at 4°C After incubation on ice for 30 min, centrifuge at 1 500 r / min for 5 min, discard the supernatant, wash twice ...

Embodiment 3

[0036] Intraperitoneal injection of cathelicidin-BF can induce up-regulation of monocyte / macrophage and neutrophil chemokines in mouse ascites:

[0037] In order to clarify that cathelicidin-BF can recruit neutrophils and monocytes / macrophages to the local peritoneal cavity, the effect of cathelicidin-BF injection on chemokines was tested. Firstly, cathelicidin-BF (10 mg / kg) was injected intraperitoneally into the mice, and the ascites was collected 4 hours later, and the levels of chemokines and cytokines were detected by ELISA.

[0038] The results showed that compared with the control group, the production levels of chemokines (CCL2, CXCL1, CXCL2) in the ascites of mice injected with cathelicidin-BF were significantly increased, which were 8.4 times, 7.8 times and 4.6 times that of the control group mice, respectively. However, the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) in ascites of mice treated with cathelicidin-BF did not change significantly ( image 3 )...

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Abstract

The invention discloses application of an innate immune activation peptide, and belongs to the technical field of biomedicine. The bungarus fasciatus antimicrobial peptide cathelicidin-BF can properlyactivate innate immune response of phagocytes of a body, but does not significantly or excessively stimulate the phagocytes to generate a lot of proinflammatory cytokines, so that the probability that a patient suffers from inflammatory immune injury is significantly reduced. In the aspect of the clinical application potentiality, the cathelicidin-BF does not have hemolytic activity or cytotoxicity, moreover, the molecular weight is small, the structure is simple, and chemical synthesis and protein expression are easy. The cathelicidin-BF has both a direct sterilization function and a function of enhancing antimicrobial innate immune response, and by means of the advantages, the cathelicidin-BF is expected to become an excellent candidate molecule for researching and developing a new generation of clinical peptide antibiotics / immunomodulators.

Description

technical field [0001] The invention relates to the application of an inherent immune activation peptide, which belongs to the technical field of biomedicine. Background technique [0002] Staphylococcus aureus (S.aureus) is the most common pathogen that causes suppurative infection in humans. It can cause local suppurative infection, and even cause pneumonia, pseudomembranous enteritis, pericarditis, and even systemic infection such as sepsis and sepsis. severe infection. Antibiotic therapy has lost its efficacy in many cases because of the emergence of methicillin-resistant S. aureus (MRSA) and insufficient development of new antibiotics against resistant bacteria. This situation has accelerated the aggressive search for new approaches to anti-infective treatments. Among new approaches being investigated, immunomodulatory therapy is an attractive approach as it can be a useful complement to antibiotic therapy and has wider application while reducing bacterial resistance....

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P31/04A61P37/04
CPCA61K38/1703A61P31/04A61P37/04Y02A50/30
Inventor 卫林徐薇周延东何小芹
Owner SUZHOU UNIV
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