FIGURE 1.

NCI cells respond to IL-36 ligands. A, IL-36γ induction of IL-6 production in NCI cells was inhibited by IL-36RA. IL-36RA was added 5 min before the addition of IL-36γ. The amount of IL-6 secreted into the cell culture medium was quantified using ELISA. NCI cells produce IL-6 at comparable levels in response to the three IL-36 cytokines. KO denotes results from the NCI-KO cell line, which has an in-frame deletion of the IL-1Rrp2 gene. B, IL-36RA can inhibit signaling by the IL-36R. Shown is IL-6 production in NCI cells treated with mock IL-36RA. IL-6 production in NCI-KO cells served as controls. All data represent the means ± S.E. for three independent experiments. C, signal transduction by the IL-36R requires MyD88. Shown is IL-6 production by NCI or NCI-KO cells knocked down for MyD88 in response to IL-36 agonists. LPS, poly(I:C), and IL-1β, which activate signal transduction by, respectively, TLR4, TLR3, and the IL-1R, served as controls for the specific effects of the IL-36 agonists in inducing IL-6 production. All data represent the mean of three independent experiments. The p values were calculated using Student's t test.