期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 78, 期 4, 页码 967-975出版社
WILEY
DOI: 10.1189/jlb.0704422
关键词
protease-activated receptors; flow cytometry; cytokines; PAR-2
Protease-activated receptor-2 (PAR-2) belongs to a family of G-coupled receptors activated by proteolytic cleavage to reveal a tethered ligand. PAR-2 is activated by trypsin and trypsin-like serine proteases and experimentally, by receptor-activating peptides (APs), which mimic the tethered ligand. PAR-2 has recently been implicated in proinflammatory immune responses. For example, PAR-2(-/-) mice exhibit markedly diminished contact hypersensitivity reactions and are completely resistant to adjuvant-induced arthritis. The present study shows that human blood monocytes express low-level cell-surface PAR-2 ex vivo, which is up-regulated upon cell purification by the mobilization of intracellular stores of PAR-2 protein. PAR-2 expression is also present on monocyte-derived macrophages, but only a small proportion of monocyte-derived dendritic cells (DC) is PAR-2(+), and blood DC are PAR(-). Freshly isolated monocytes responded to the PAR-2 AP ASKH 95 (2-furoyl-LIGKV-OH) with the generation of a calcium flux and production of interleukin (IL)-1 beta, IL-6, and IL-8. The results presented thus suggest that PAR-2 contributes to inflammatory responses by inducing the production of proinflammatory cytokines in peripheral blood monocytes.
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