Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages

Figure 5 Gasdermin D knockout significantly decreases the expression of monocyte chemotactic protein 1/ CC chemokine receptor-2 and macrophage infiltration in D-galactose/lipopolysaccharide-induced acute liver failure mice. A: Protein expression levels of cleaved N-terminal fragment of gasdermin D, monocyte chemotactic protein 1 (MCP1), and CC chemokine receptor-2 in the liver evaluated by Western blot; B: Immunohistochemical staining for macrophage-specific F4/80 in the liver. Scale bars = 100 µm; C: Detection of serum MCP1, interleukin (IL)-1β, IL-18, tumor necrosis factor-alpha, and interferon-γ by enzyme-linked immunosorbent assay; D: The diagram showing the mechanism of hepatocyte pyroptosis for expanding the inflammatory responses; Data are presented as the mean ± square error. ^aP < 0.05, ^bP < 0.01, and ^eP < 0.001. WT: Wild type; GSDMD-/-: GSDMD genetic knockout; D-Galn/LPS: D-galactose/lipopolysaccharide; PBS: Phosphate buffer saline; GSDMD-N: Cleaved N-terminal fragment of GSDMD; MCP1: Monocyte chemotactic protein 1; CCR2: CC chemokine receptor-2; IL-1β: Interleukin-1β; IL-18: Interleukin-18; TNFα: Tumor necrosis factor-alpha; IFNγ: Interferon-γ.