Extended Data Fig. 8: Colchicine-induced GDF15 inhibits pro-IL-1β expression by activating the immuno-inhibitory signal of SHP-1 in primary neutrophils.
From: Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activation
Ex vivo activation of neutrophils evaluated by the levels of (a-b) pro-IL-1β induction or (c-d) phosphorylated SHP-1. Cells were pre-incubated with plasma from the indicated mice and then activated with PMA. a, Induction of GDF15 specifically in hepatocytes was required for the anti-inflammatory activity of post-colchicine plasma, as assayed by pro-IL-1β induction. GalNAc-siLuc, hepatocyte-specific siRNA against luciferase. GalNAc-siGDF15, hepatocyte-specific siRNA against GDF15. b, The anti-inflammatory activity of post-colchicine plasma was blocked by two different clones of antibodies (#2 and #3) against GDF15. ctr, control antibody. veh plasma, plasma from vehicle-treated mice. Colc plasma, plasma from colchicine-treated mice. c, GDF15 neutralization by two clones of anti-GDF15 antibodies (#2 and #3) blocked plasma activity on stabilizing SHP-1 activation. d, Expression of colchicine-induced GDF15 specifically in hepatocytes was required for activating SHP-1. 3 Biological replicates.
