Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH2, and PAR-2 agonist peptide tc-LIGRLO-NH2 provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH2-induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH2, an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH2-induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.

Altered Expression of IFN-λ2 in Allergic Airway Disorders and Identification of Its Cell Origins.

This study investigated the expression levels of interferon- (IFN-) λ2 in peripheral blood and tissues. The results showed that the levels of IFN-λ2 were elevated by 17.9% and 14.2% in the plasma of allergic rhinitis (AR) and combined rhinitis with asthma (AR + AS), which was positively correlated with the level of tryptase but negatively correlated with the level of IL-10. IFN-λ2 was predominately expressed in the CD16+ cells and CD14+ cells in healthy control subjects (HC) but upregulated only in CD8+ cells of AR and in eosinophils of asthma. It was observed that approximately 6.6% and 7.0% dispersed tonsil cells and 5.8% and 0.44% dispersed lung cells are IFN-λ2+ mast cells and macrophages. Moreover, tryptase and agonist peptides of PAR-2 induced enhanced IFN-λ2 mRNA expression in A549 cells. In conclusion, the elevated levels of IFN-λ2 in the plasma of AR and AR + AS indicate that IFN-λ2 is likely to contribute to the pathogenesis of allergic airway disorders. The potential origins of the elevated plasma IFN-λ2 include mast cells, macrophages, and epithelial cells in tissues, neutrophils, monocytes, CD8+ T cells, and eosinophils in peripheral blood. Development of IFN-λ2 related therapy may help to treat or prevent allergic airway disorders.