Interleukin-33 promotes type 1 cytokine expression via p38 MAPK in human natural killer cells

David E. Ochayon; Ayad Ali; Pablo C. Alarcon; Durga Krishnamurthy; Leah C. Kottyan; Michael Borchers; Stephen N. Waggoner

Next, we sought to examine whether nearphysiological concentration of IL-33 could provoke enhanced IFN- expression in IL-12 stimulated NK cells. Isolated NK cells secreted IFN- in response to doses of IL-12 as low as 250 pg/mL ( Fig. 2A) . In contrast, production of IFN- by these cells was barely detectable after stimulation with IL-33 alone, even at doses as high as ≥1 ng/mL ( Fig. 2A) . However, 100 pg/mL or more of IL-33 enhanced (1.7-to 2.9fold) IL-12-elicited IFN- protein expression ( Fig. 2A) , with synergistic interactions between IL-12 and IL-33 contributing significantly (p<0.0001, two-way ANOVA) to the overall variation in IFN- expression. High concentrations of IL-33 (10 ng/mL) additionally provoked expression of TNF and GM-CSF when administered in combination with IL-12 (Fig. 2B) . The bulk of variation in the expression of TNF (p=0.011, two-way ANOVA) and GM-CSF (p=0.0008, two-way ANOVA) were attributable to synergistic interactions between IL-33 and IL-12 (Fig. 2B) .