Fig. 10
Potential involvement of ANGPTL8 in the acute inflammation caused by infection. a The upregulation and downregulation rate of Tnfa transcription during the acute phase (0–1 h) and the resolution phase (1–6 h) upon LPS infection. The upregulation rate was determined by the fold change between 0–1 h, while the downregulation rate was determined by the fold change per hour between 1–6 h after the injection. (n = 3 for 0 and 1 h, n = 4 for 6 h). b, c The immunoblots (b) and quantitation results (c) of the expression of Ikkγ and Angptl8 in the liver upon LPS infection. Each lane stands for one mouse. d Angptl8 forms a complex with Ikkγ and p62 upon LPS infection. Equal amount of lysate obtained from each animal at the same time point were mixed, and subjected to Co-IP experiment (n = 3 for 0 and 1 h, n = 4 for 6 h). e The circulating ANGPTL8 was elevated in patients with positive detection of PCT or endotoxin (healthy control, n = 30; PCT, n = 18; endotoxin, n = 10). f A working model of ANGTPL8 mediated regulation of TNFα-induced signaling. TNFα upregulates the expression of ANGPTL8, and then aggregated ANGPTL8 facilitates the ANGPTL8-p62-IKKγ complex formation, which promotes the autophagic IKKγ degradation and inhibits TNFα-induced NF-κB activation. Data are shown as the mean ± SEM in c, e, unpaired two-tailed Student’s test was used for statistics. ***p < 0.0001, **p < 0.01, *p < 0.05
