Fig. 4: Selective CXCL1 neutralization alleviates the severity of RILD through hampering neutrophil recruitment. | Nature Communications

Fig. 4: Selective CXCL1 neutralization alleviates the severity of RILD through hampering neutrophil recruitment.

From: Gasdermin D aggravates a mouse model of radiation-induced liver disease by promoting chemokine secretion and neutrophil recruitment

Fig. 4

A Volcano plot depiction of neutrophil chemokine genes between GsdmdFL/FL and Gsdmd∆Hep mice (n = 5/group). B Detection of the hepatic mRNA level of Cxcl1 in GsdmdFL/FL and Gsdmd∆Hep mice (n = 5/group) accepted or were free of 30 Gy or 6 Gy×5 IR. ***p = 0.001, ST: GsdmdFL/FL-Ctrl vs Gsdmd∆Hep; *p = 0.01, LT: GsdmdFL/FL-Ctrl vs Gsdmd∆Hep. C Representative immunohistochemistry images of CXCL1 in liver tissue of Ctrl and IR group from GsdmdFL/FL and Gsdmd∆Hep mice (Scale bars, 40×, 200 μm; 400×, 50 μm, left). Statical analysis of CXCL1 expression were calculated from five fields per liver (n = 5/group, right). ****P < 0.0001. D Representative liver CXCL1 staining from ST-RILD mice treated with AAV9-control and AAV9-GSDMD-FL adeno virus (Scale bars, 40×, 200 μm, left). Statical analysis of CXCL1 expression were calculated from five fields per liver (n = 4/group, right). ****P < 0.0001. E Detection of the neutrophil infiltration in liver of mice treated with isotype IgG antibody and anti-CXCL1 antibody. The percentage of cells with CD11b+Ly6G+ with flow cytometry (left) and its statical analysis were presented in both ST- and LT-RILD cohort (right; n = 3 mice/group, ST; n = 5 mice/group, LT). **p = 0.008, ST: isotype IgG vs anti-CXCL1 Ab; *p = 0.03, LT: isotype IgG vs anti-CXCL1 Ab. F Representative liver HE images from ST-RILD mice (Scale bars, 200×, 50 μm). G–I Representative liver macroscopic images (G), ɑ-SMA staining (H, p = 0.0002) and sirius-red staining (I, p = 0.0039) in cohort of LT-RILD mice. (Scale bars, 400×, 50 μm). Statistical analysis of ɑ-SMA and collagen area were present in the right, 5 fields were observed per mice. (F-I, n = 3/group). J Hepatic mRNA levels of Col1a1 (p = 0.0169), Tgfb1 (p = 0.044) and Timp1 (p = 0.0478) from LT-RILD mice. K Imunoblot analysis of COL1A1, Fibronectin and ɑ-SMA. n = 5/group for J-K. L Serum levels of ALT, AST, and ALB (n = 3/group, isotype-ST; n = 5/group, anti-CXCL1 Ab and isotype-LT). ST-isotype IgG vs anti-CXCL1 Ab: ALT, p = 8.27E-07; AST, p = 0.000219; ALB, p = 0.0068. LT-isotype IgG vs anti-CXCL1 Ab: ALT, p = 9.72E-07; AST, p = 1.52E-05; ALB, p = 0.0016. p values were using two-way ANOVA with Fisher’s LSD multiple comparisions test (C, L) and unpaired two-sided Student’s t test (B, D, E and H–J). Data are expressed as mean ± SEM. No data were excluded from the analyses. Source data are provided as a Source Data file.

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