Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway.

Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2.

Rapid up-regulation of CXC chemokines in the airways after Ag-specific CD4+ T cell activation.

Ag-specific activation of CD4(+) T cells is known to be causative for the cytokine production associated with lung allergy. Chemokine-induced leukocyte recruitment potentially represents a critical early event in Ag-induced lung inflammation. Whether Ag-specific, lung CD4(+) T cell activation is important in lung chemokine production is currently not clear.

Airway inflammation driven by antigen-specific resident lung CD4(+) T cells in alphabeta-T cell receptor transgenic mice.

CD4(+) T cells are thought to play a major role in the initiation and perpetuation of T helper cell, type 2 (Th2)-like allergic airway inflammation. However, it is not clear whether activation of resident antigen-specific CD4(+) T cells is in itself sufficient to induce such a phenotype. Using ovalbumin (OVA)-specific alphabeta-T cell receptor transgenic Balb/c DO11.

Ro 45-2081, a TNF receptor fusion protein, prevents inflammatory responses in the airways.

The TNF receptor fusion protein, Ro 45-2081, inhibited allergic and non-allergic inflammatory responses in the airways. Treatment of sensitized guinea-pigs with Ro 45-2081 reduced allergen-induced influx of inflammatory cells into the lungs, abolished edema formation and inhibited hyperreactivity to substance P. Administration of Ro 45-2081 after allergen challenge reversed the influx of inflammatory cells into the lungs.