TY - EJOU AU - Westphal, Elena AU - Herzberg, Mona AU - Neumann, Ingo AU - Beibei, Li AU - Pilowski, Claudia AU - Li, Chen AU - Werdan, Karl AU - Loppnow, Harald TI - Neutrophils process interleukin-1β and interleukin-18 precursors in a caspase-1-like fashion – processing is inhibited by human vascular smooth muscle cells T2 - European Cytokine Network PY - 2006 VL - 17 IS - 1 SN - 1952-4005 AB - Inflammation contributes to the pathogenesis of atherosclerosis. Proinflammatory cytokines, including interleukin-1 (IL-1), may be involved in the local inflammation occurring in the vessel wall. Vascular smooth muscle cells express the unprocessed IL-1β precursor molecule. Invading leukocytes, such as monocytes or polymorphonuclear granulocytes (PMN) may activate the IL-1β precursor during atherogenesis. Thus, we investigated the capacity of PMN to process IL-1β and IL-18 precursors. Processing was analyzed using Western blot and bioassay for IL-1-activity was performed. As few as 80 to 400 PMN/mL detectably processed preIL-1β. PMN also cleaved the caspase-1 substrate preIL-18. The preIL-1β and preIL-18 cleavage products were located at the same apparent molecular weight as those resulting from cleavage by monocyte-derived caspase-1. PMN expressed caspase-1 mRNA and immunoreactive protein. The N-terminus of the preIL-1b cleavage product expressed the sequence expected for caspase-1 cleavage. The cleavage product was active in the bioassay for IL-1 activity, and the caspase-1 inhibitor YVAD blocked processing. We have shown previously that SMC can block processing of preIL-1 by caspase-1. In contrast, SMC do not block processing of PARP by caspase-3. Here, we show that SMC also inhibited the PMN-mediated processing of recombinant and native preIL-1β or preIL-18 depending on the cell number, whereas EC or fibroblasts did not block processing. Our results indicate that PMN can activate preIL-1β in a caspase-1-like fashion. During inflammatory processes, PMN may activate preIL-1β released from SMC, thereby altering IL-1-mediated cardiovascular functions, including contractility, apoptosis, and cytokine production. KW - human KW - neutrophils KW - monocytes/macrophages KW - cytokines KW - inflammation DO -