(A) Extent of in vitro deletion of IRE1α (Ern1) by treating Ern1fl/fl BMDCs with the cell-permeable Cre recombinase HTNC, as measured by quantitative PCR (n=3). (B) IRE1α-deficient BMDCs from (A) exhibit reduced IL-1β secretion when stimulated by SFAs (500 μM, 20 h) but not by ATP (n=2–3). (C) Partial deletion of IRE1α in Cd11b-Cre+/Ern1fl/fl BMDCs also modestly diminishes IL-1β secretion stimulated by PA (500 μM, 24 h) but not by ATP (n=4). (D) Efficacy of IRE1α endonuclease inhibitors STF083010 (200 μM) and 4μ8C (50 μM) in reducing IRE1α reporter activation by 24 h treatment with PA (1 mM), SA (500 μM), or classical ER stress inducers (n=6). (E). STF083010 (200 μM) and 4μ8C (200 μM) abrogate IL-1β secretion stimulated by SFAs (500 μM, 24 h) but not ATP (n=3). Error bars, SD. *, p<0.05 vs. WT + HTNC (A,B), Ern1fl/fl (C), or vehicle (D,E). See also Figure S4.