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Antimicrobial effects of vertebrate TFPI-2 C-terminal peptides

Published: 2016-11-30

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Article from our customer: Kasetty et al. BMC Microbiology (2016) 16:129

 

Background: In previous studies we reported a novel role of human tissue factor pathway inhibitor-2 (TFPI-2) in innate immunity by serving as a precursor for host defense peptides. Here we further studied the therapeutic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model.
Results: A number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E.coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement.
Conclusion: Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies.

Fig.6 Treatment of LPS-induced septic shock mice with a mouse TFPI-2 derived peptide. Septic shock in Balb/c mice was induced by i.p. injection of 10 mg/kg E. coli LPS. Thirty minutes after LPS injection, VKG24 (0.5 mg/mouse or ~25 mg/kg body weight) or PBS was administratedi.p. (a)Mouse TFPI-2 derived peptide significantly increased survival of mice. Survival of mice was monitored for 7 days (only the first 96 h is shown in the figure). Statistical comparisons of survival curves were performed using the Mantel-Cox’s test. ***P ≤ 0.0003. (b)Weight was determined daily. (c)Clotting times of aPTT and PT was measured in citrate plasma 24 h after LPS injection (n = 8). (d)The indicated cytokines were analyzed in plasma 24 h after LPS injection (n = 8). Statistical analysis for C-D, one-way ANOVA with Tukey’s multiple comparisons post-test was used. **P ≤ 0.003, ****P ≤ 0.0001

 

All of the peptides used in this article were synthesized by Ontores (Shanghai, China). The purity (>98 %) of these peptides was confirmed by mass spectral analysis (MALDI-TOF Voyager).