Fig. 7

IL-6 deficiency attenuates neuroinflammation in 5×FAD mice via the STAT3-cGAS-STING pathway. (A-B) qRT-PCR analysis of Cgas (A) and Sting (B) mRNA levels relative to Gapdh in hippocampal tissue from 6-month-old 5×FAD mice compared to WT mice. (C-D) qRT-PCR analysis of Cgas (C) and Sting (D) mRNA levels relative to Gapdh in hippocampal tissue from 6-month-old Il6^−/−:5×FAD mice compared to 5×FAD mice. (E-F) Peak distribution of STAT3 binding within the promoter regions of Cgas (E) and Sting (F), visualized using the Integrative Genomics Viewer (IGV) after ChIP-seq experiments on hippocampal tissues from 5×FAD and Il6^−/−:5×FAD mice. (G-H) ChIP-qPCR of hippocampal tissues from 5×FAD (G) and Il6^−/−:5×FAD mice (H) using a STAT3 antibody and isotype control IgG to evaluate fold enrichment levels on the Cgas and Sting gene fragments. (I) Western blot analysis of p-STAT3, STAT3, cGAS, and STING in BV2 cells treated with different concentrations of mIL-6 or Aβ42 for 24–48 h. (J-L) qRT-PCR analysis of mRNA levels of Cgas (J), Sting (J), Il1b (K), Ifnb1 (L), and ISGs (Isg15, Isg20, Ifit1, Ifit2) (L) relative to Gapdh in BV2 cells treated with mIL-6 (5000 pg/mL) and Aβ42 (10 µM or 20 µM) for 48 h. For panels (A-D), n = 5 mice per group (mixed sexes), with each dot representing a mouse. For panels (E-H), n = 1 mouse per group. For panels (G-H) and (J-L), each dot represents a well. For panel (I), each lane represents a group. Data are presented as mean ± S.E.M. Statistical significance was determined using Student’s t-test or Welch’s t-test for panels (A-D) and (G-H), and one-way ANOVA followed by Tukey’s multiple comparisons test or the Games-Howell test for panels (J-L). Significance levels are indicated as follows: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; ns indicates not significant