Fig. 4: Effects of the stapled peptide on endotoxin responses in experimental mouse models. | Nature Communications

Fig. 4: Effects of the stapled peptide on endotoxin responses in experimental mouse models.

From: Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs

Fig. 4

a A representative in vivo inflammation imaging by IVIS in NF-κB reporter mice. HVF18 or sHVF18 were mixed with LPS immediately before subcutaneous injection on the back of transgenic BALB/c Tg(NF-κB-RE-luc)-Xen reporter mice. In vivo imaging was performed using an IVIS Spectrum bioimaging system at 3–6–24 h after subcutaneous deposition. The bar chart shows the measured bioluminescence intensity emitted from these mice. Data are presented as the means ± SEM; 3h: LPS group (n = 7), LPS + HVF18 group (n = 5), LPS + sHVF18 group (n = 7); 6 h: LPS group (n = 7), LPS + HVF18 group (n = 6), LPS + sHVF18 group (n = 7);. 24 h: LPS group (n = 6), LPS + HVF18 group (n = 6), LPS + sHVF18 group (n = 6). P values were determined using a one-way ANOVA with Tukey’s multiple comparisons tests. b, Cytokines release from plasma collected after 8 and 20 h from C57BL/6 mice stimulated with a sublethal dose of LPS and then treated with sHVF18. Data for the bar charts are presented as the means ± SEM. For 8 h: LPS group (n = 21), LPS + 50 µg sHVF18 group (n = 10), LPS + 100 µg sHVF18 group (n = 11), 50 µg sHVF18 group (n = 5), 100 µg sHVF18 group (n = 5), control (n = 9); 20 h: LPS group (n = 22), LPS + 50 µg sHVF18 group (n = 10), LPS + 100 µg sHVF18 group (n = 22), 50 µg sHVF18 group (n = 5), 100 µg sHVF18 group (n = 5), control (n = 10). P values were determined using ordinary one-way ANOVA following Dunnett’s multiple comparisons tests. c Representative images show H&E staining of mouse lung tissue at 8 and 20 h in a mouse model of LPS-induced sepsis. Arrowheads indicate areas of immune cell invasion and hyper-inflammatory condition of the lung tissue. d Bar chart depicts lung injury scores based on histological analysis of the lung tissues. Data are presented as the mean ± SEM; control group (n = 8), all the other groups (n = 10). P values were determined using a one-way ANOVA with Tukey’s multiple comparisons test. e Representative scanning electron microscopy images showing changes in the lung tissue 20 h after i.p. LPS administration alone or after peptide treatment.

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