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Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway.

Yu HS, Angkasekwinai P, Chang SH, Chung Y, Dong C - J. Korean Med. Sci. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Pusan National University Hospital Medical Research Institute, School of Medicine, Pusan National University, Busan, Korea.

ABSTRACT
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.

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IL-25 and TSLP gene expression of various cells is induced by protease allergens. (A) IL-25 expression of PLE (primary lung epithelial cell) and (B) IL-25 and TSLP expression of MEF cells are induced by protease stimulations. (C) Additionally, the eotaxin gene expression of MLE12 cells is induced by protease stimulations (*P<0.05).
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Figure 3: IL-25 and TSLP gene expression of various cells is induced by protease allergens. (A) IL-25 expression of PLE (primary lung epithelial cell) and (B) IL-25 and TSLP expression of MEF cells are induced by protease stimulations. (C) Additionally, the eotaxin gene expression of MLE12 cells is induced by protease stimulations (*P<0.05).

Mentions: In order to determine whether the induction of the Th2-type response is a common feature of protease allergens, we subsequently measured the levels of IL-25 and TSLP in the MLE12 mouse lung epithelial cell line after stimulation with a variety of allergens. Consistent with the data shown in Fig. 1, papain treatment triggered the expression of IL-25 and TSLP mRNA in the MLE12 cells (Fig. 2A). These effects were inhibited by the deactivation of the protease activity of papain, either by boiling or by treatment with protease inhibitors (Fig. 2A). It is worth noting that Aspergillus protease (Asp) and DerP1, both of which are known as strong allergens with protease activity, also induced the expression of IL-25 and TSLP (Figs. 2B, C). The induction of IL-25 and TSLP by these allergens was also noted in primary lung epithelial (PLE) cells and mouse embryonic fibroblast (MEF) cells (Fig. 3A, B). The protease allergens also induced the expression of Th2-associated chemokine genes, particularly the eotaxin gene (Fig. 3C).


Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway.

Yu HS, Angkasekwinai P, Chang SH, Chung Y, Dong C - J. Korean Med. Sci. (2010)

IL-25 and TSLP gene expression of various cells is induced by protease allergens. (A) IL-25 expression of PLE (primary lung epithelial cell) and (B) IL-25 and TSLP expression of MEF cells are induced by protease stimulations. (C) Additionally, the eotaxin gene expression of MLE12 cells is induced by protease stimulations (*P<0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2877219&req=5

Figure 3: IL-25 and TSLP gene expression of various cells is induced by protease allergens. (A) IL-25 expression of PLE (primary lung epithelial cell) and (B) IL-25 and TSLP expression of MEF cells are induced by protease stimulations. (C) Additionally, the eotaxin gene expression of MLE12 cells is induced by protease stimulations (*P<0.05).
Mentions: In order to determine whether the induction of the Th2-type response is a common feature of protease allergens, we subsequently measured the levels of IL-25 and TSLP in the MLE12 mouse lung epithelial cell line after stimulation with a variety of allergens. Consistent with the data shown in Fig. 1, papain treatment triggered the expression of IL-25 and TSLP mRNA in the MLE12 cells (Fig. 2A). These effects were inhibited by the deactivation of the protease activity of papain, either by boiling or by treatment with protease inhibitors (Fig. 2A). It is worth noting that Aspergillus protease (Asp) and DerP1, both of which are known as strong allergens with protease activity, also induced the expression of IL-25 and TSLP (Figs. 2B, C). The induction of IL-25 and TSLP by these allergens was also noted in primary lung epithelial (PLE) cells and mouse embryonic fibroblast (MEF) cells (Fig. 3A, B). The protease allergens also induced the expression of Th2-associated chemokine genes, particularly the eotaxin gene (Fig. 3C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Pusan National University Hospital Medical Research Institute, School of Medicine, Pusan National University, Busan, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus