Proposed role for caspase-8 in monocytes undergoing macrophagic differentiation. Exposure of primary monocytes to M-CSF or U937 cells to TPA triggers caspase-8 interaction with FADD, FLIP, and RIP1. Caspase-8 is activated in this multimolecular platform, which induces the cleavage of RIP1. In turn, RIP1 cleavage fragment could down-regulate NF-κB activity. Caspase-8 may also activate downstream caspases that could further contribute to the differentiation pathway by cleaving other cellular targets.