Volume 7 Supplement 1
Tryptase as a PAR-2 activator in joint inflammation
© BioMed Central Ltd 2005
Received: 11 January 2005
Published: 17 February 2005
Protease-activated receptor-2 (PAR-2) is one of a family of G-protein coupled transmembrane receptors activated by proteolytic release of a 'tethered' ligand. We previously reported this receptor has a pivotal role in chronic joint inflammation using a PAR-2 'knockout' mouse , but the serine protease responsible for its activation remains uncertain.
We investigated whether β-tryptase has proinflammatory actions in the mouse knee and specifically whether a tryptase inhibitor can modulate experimentally induced chronic joint inflammation.
Five micrograms of human β-tryptase was injected into the knee joint cavity of two groups of anaesthetized (Halothane/O2/N2O) mice (30 g): wild-type (PAR-2+/+) C57BL/6J mice and PAR-2 gene disrupted mice (PAR-2-/-). Joint swelling was assessed by comparing caliper measurements of knee joint diameter pre-injection and post-injection. Chronic monoarthritis was induced using the same anaesthetic regime in separate wild-type mice by intra-articular and peri-articular injection of Freunds complete adjuvant (FCA) (in 5% methycellulose). In a parallel group of mice, 50 μg of the tryptase inhibitor 4-amidino phenyl pyruvic acid (APPA) was co-administered with the FCA/methycellulose emulsion. Joint diameter was measured over 10 days.