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. Author manuscript; available in PMC: 2020 Aug 12.
Published in final edited form as: Cell Chem Biol. 2020 Jan 2;27(1):94–104.e5. doi: 10.1016/j.chembiol.2019.12.007

Figure 3. The cIAP inhibitor LCL161 solicits interleukin-12 expression through the non-canonical NFkB pathway.

Figure 3.

a, Representative image of IL-12-eYFP BMDC. b, Correlation of YFP levels with IL-12p40 production. Stimulating BMDCs with increasing doses of LCL161 (100 nM to 10 μM at 1/4 log titration) upregulates the eYFP reporter, which correlates with endogenous IL-12p40 levels, as measured by indirect immunofluorescence for IL-12p40. Black line: linear regression ± 95% CI (dotted line). c, LCL161 (0.316 μM, 1 day) elevates/raises IL-12p40 in both bone marrow-derived dendritic cells and macrophages, though more so in dendritic cells. Data reported as mean ± s.d.; n=2 or 3, as indicated on plot. d, Cartoon schematic of non-canonical NFkB pathway. LCL161 inhibits the cIAP E3 ligase complex, preventing ubiquitination of NIK, thereby blocking proteasomal degradation. This increases NIK, which leads to nuclear translocation of the active p52 and RelB NFkB subunits. This in turn causes IL-12 production. e, The response to LCL161 (doses indicated, 1 day) in NIK KO BMDCs is markedly reduced compared to WT BMDCs.