the decreased response to MDP in CD. There was no detectable phospho-p38 in unstimulated controls and CD patients with or without CD associated CARD15 variants. Hederagenin stimulation with MDP highly activated the p38 MAPK as seen by increased amounts of phospho-p38. Interestingly, this increase was found in both control and CD monocytes regardless of CARD15 status. Thus no major differences were found between control and CD in activation of the p38 pathway. Contrary to CD monocytes, control monocytes had an increased IKKa/b phosphorylation without stimulation. The IKKa/b phosphorylation increased substantially in MDP stimulated control monocytes compared to CD monocytes, which had low or no detectable IKKa/b phosphorylation upon MDP stimulation. No significant differences were seen between CD monocytes regardless of CARD15 variant status. This suggests that lack of NFkB activation by MDP in CD could explain the decreased response to MDP. 183204-72-0 chemical information Caspase 1 protein was constitutively highly expressed in CD monocytes, and was cleaved to its active form in unstimulated cells. No increases in the expression level or cleavage of caspase 1 were seen upon stimulation with MDP neither in CD nor in controls. Monocytes expressed the proteins of the NALP3- inflammasome on the protein level: NALP3, ASC, and CARD8. Released activated caspase 1 to the media was, however, equal in CD and control. As described earlier the basal level of pro-IL-1b was increased in CD compared to controls. The amount of matured IL-1b was also increased in CD, but in all cases IL-1b protein expression was independent of MDP stimulation. The release of mature IL-1b was also independent on disease stage and MDP stimulation and equal in CD and control monocytes. This suggests that the inflammasome is constitutively active in CD, but that the inflammasome activity is not dependent on MDP stimulation in human monocytes, neither in controls, nor in CD. The constitutively active caspase 1 found in CD explain the increased expression of mature IL-1b in CD compared to control monocytes. We describe an impaired response to MDP in monocytes from CD patients without disease linked CARD15 variants. The dysfunctional respon