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. 2020 May 4;130(6):3021–3037. doi: 10.1172/JCI125505

Figure 9. Gas6/Axl axis suppresses IL-18 production from macrophages by suppressing the activation of caspase-1 and NF-κB.

Figure 9

(A) The levels of IL-18 in the BAL fluid on day 1 after S. pneumoniae infection after RSV infection in various treatment groups (WT vs. Gas6–/–; WT vs. Axl–/–; IgG vs. Axl mAb treatment; hydroxypropyl methylcellulose vs. BGB324 treatment; PBS vs. rGas6 treatment; and control liposome vs. clodronate liposome treatment). The levels of IFN-γ, NO, and TNF-α in the BAL fluid from each group at day 1 after S. pneumoniae infection in the anti–IL-18 mAb-treated (B) and recombinant IL-18–treated (C) mice infected with S. pneumoniae and/or RSV. (D and E) IL-18 production in the alveolar macrophages isolated from WT and Gas6–/– mice on day 8 after RSV infection and stimulated with S. pneumoniae for 1 hour. (F) Activation of caspase-1 and degradation of IκB in the alveolar macrophages isolated from WT and Gas6–/– mice on day 8 after RSV infection and stimulated with S. pneumoniae for 3 hours (left panel). The ratios of cleaved caspase-1 (p10) and the IκB to GAPDH ratio are shown (right panel). The data are expressed as mean ± SEM; n = 4–6 (A and B), n = 2–3 (E and F). Representative results from 2 independent experiments are shown. The following statistical tests were used: 2-tailed Student’s t-test (A, for WT vs. Gas6–/–; WT vs. Axl–/–; IgG vs. Axl mAb treatment; hydroxypropyl methylcellulose vs. BGB324 treatment), and 1-way ANOVA (A, for PBS vs. rGas6 treatment; and control liposome vs. clodronate liposome treatment, B, C, and E). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.