@Article{,
AUTHOR = {Elena Westphal, Mona Herzberg, Ingo Neumann, Li Beibei, Claudia Pilowski, Chen Li, Karl Werdan, Harald Loppnow},
TITLE = {Neutrophils process interleukin-1β and interleukin-18 precursors in a caspase-1-like fashion – processing is inhibited by human vascular smooth muscle cells},
JOURNAL = {European Cytokine Network},
VOLUME = {17},
YEAR = {2006},
NUMBER = {1},
PAGES = {19--28},
URL = {http://www.techscience.com/ECN/v17n1/66164},
ISSN = {1952-4005},
ABSTRACT = {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.},
DOI = {}
}