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Human peripheral blood monocytes express protease receptor‐2 and respond to receptor activation by production of IL‐6, IL‐8, and IL‐1β
Author(s) -
Johansson Ulrika,
Lawson Charlotte,
Dabare Michael,
SyndercombeCourt Denise,
Newland Adrian C.,
Howells Gareth L.,
Macey Marion G.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0704422
Subject(s) - proinflammatory cytokine , biology , monocyte , proteases , receptor , protease activated receptor 2 , serine protease , immune system , microbiology and biotechnology , immunology , inflammation , protease , biochemistry , enzyme , 5 ht5a receptor
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)‐1β, 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.