Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-? pathway.

ABSTRACT: The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-?. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-? production by alveolar macrophages through the PAR-2 pathway and whether the TNF-? production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-? production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-?. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-? production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-? blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-? level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-? dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.

SUBMITTER: Kim JY 

PROVIDER: S-EPMC3477122 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature