Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway.
Allergic diseases, including asthma, are characterized by T helper type 2 (Th2) cell-mediated inflammations, coupled with tissue infiltration by eosinophils. In this study, we demonstrate that multiple protease allergens, including papain and DerP1, efficiently induce interleukin (IL)-25 and thymic stromal lymphopoietin (TSLP) gene expression, and this phenomenon is dependent on the protease activities of these allergens. The IL-25 cytokine level in bronchial alveolar lavage (BAL) was also profoundly and significantly increased after treatment with papain. Additionally, the levels of Th2 cytokines were significantly increased, as compared to those in the OVA-only treatment group. The various protease allergens triggered the expression of IL-25 and TSLP mRNA in mouse lung epithelial cells (MLE12) and primary mouse lung epithelial cells; these effects were inhibited by the deactivation of the protease activity of papain. The allergen papain activates the ErK and p38 MAP pathways; the inhibition of these pathways, but not the NFkappaB or PI-3 kinase pathways, impairs the induction of IL-25 and TSLP expression by proteases. In this study, we demonstrate that the protease allergens induce IL-25 and TSLP via the MAP kinase signal pathways, and their protease activities are essential to this pathway.
Department of Parasitology, Pusan National University Hospital Medical Research Institute, School of Medicine, Pusan National University, Busan, Korea.
Hak Sun
HS
Yu
Pornpimon
P
Angkasekwinai
Seon Hee
SH
Chang
Yeonseok
Y
Chung
Chen
C
Dong
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010206:Papain / Q000494:pharmacology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; D020381:Interleukin-17; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010206:Papain; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse