Fig. 5 | Signal Transduction and Targeted Therapy

Fig. 5

From: Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages

Fig. 5

Stearic acid stimulates macrophage activation in vitro via TLR4. a The Toll-like receptor signaling pathway was highly enriched in the eFats of tumor-seeded mice treated with a CD or HFD for 5 days. Six-week-old male mice were intraperitoneally injected with MC-38 cells (1.0 × 106 cells in 100 µl PBS) and immediately fed a CD or HFD for 5 days. Then the eFats were collected for RNA sequencing assays, and altered gene expression was subjected to KEGG pathway enrichment analysis. b Fold changes in gene expression determined by comparing RNA sequencing results between the CD group and the HFD group. Red points indicate upregulated genes; blue points indicate downregulated genes; gray points show unchanged genes. Toll-like receptor 4 (TLR4) expression was obviously upregulated by HFD consumption. c The level of free fatty acid (FFA) in eFats of the mice treated with CD or HFD for 5 days. d Stearic acid and LPS stimulate TLR4-dependent phagocytosis in macrophages. Peritoneal macrophages from wild-type (WT) or TLR4 knockout (TLR4-ko) mice were pretreated with stearic acid (SA; 200 µM) and/or LPS (100 ng ml−1) for 12 h and cocultured with GFP-tagged MC-38 cells for phagocytosis assays. This experiment was repeated twice. Representative results are displayed. e Statistical analysis of the results in d. Data are presented as the mean ± s.e.m. (n = 3; *P < 0.05 and **P < 0.01; Student’s t test). fh A fatty acid stimulates TLR4-dependent proinflammatory cytokine expression. Peritoneal macrophages from WT or TLR4-ko mice were treated with SA (200 µM) or LPS (100 ng ml−1) for 6 h, and then RNA was extracted for real-time PCR analysis of TNFα, IL-1β, and Cxcl10. Data are presented as the mean ± s.e.m. (n = 3; ***P < 0.005; Student’s t test)

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