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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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Protease allergens induce IL-25 and TSLP expression via the MAP kinase pathway. (A) Erk, JNK, and p38 MAP kinase pathways were activated via papain treatment. (B) However, boiled papain did not activate the Erk or p38 MAP kinase pathways. (C) The induction of IL-25 and TSLP of MEF cells by papain treatment is inhibited by MAP kinase inhibition. (D) The IL-25 gene expression of MyD88& TIRA-/- MEF after papain treatment is similar to that of wild type MEF. Protease allergen-induced IL-25 expression was not mediated via the MyD88 or TIRAP pathways. I-pI3K, inhibitor of pI3 kinase (LY294002); I-Erk, inhibitor of Erk MAPK (PD98059); I-p38, Inhibitor of p38 MAPK (SB203580); I-JNK, Inhibitor of JNK MAPK (JNK inhibitor II) (*P<0.05).
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Figure 4: Protease allergens induce IL-25 and TSLP expression via the MAP kinase pathway. (A) Erk, JNK, and p38 MAP kinase pathways were activated via papain treatment. (B) However, boiled papain did not activate the Erk or p38 MAP kinase pathways. (C) The induction of IL-25 and TSLP of MEF cells by papain treatment is inhibited by MAP kinase inhibition. (D) The IL-25 gene expression of MyD88& TIRA-/- MEF after papain treatment is similar to that of wild type MEF. Protease allergen-induced IL-25 expression was not mediated via the MyD88 or TIRAP pathways. I-pI3K, inhibitor of pI3 kinase (LY294002); I-Erk, inhibitor of Erk MAPK (PD98059); I-p38, Inhibitor of p38 MAPK (SB203580); I-JNK, Inhibitor of JNK MAPK (JNK inhibitor II) (*P<0.05).

Mentions: In an effort to address the intracellular mechanism that regulates IL-25 and TSLP expression upon stimulation with protease allergens, we evaluated the activation of intracellular MAPK and NF-κB. Papain induced the phosphorylation of ERK, JNK, and p38 MAPK in MEF cells within as short a time as 15 min (Fig. 4A). Boiled papain marginally induced p-JNK with delayed kinetics, and failed to induce the phosphorylation (Fig. 4B). On the other hand, the levels of IκBα were reduced 2 hr after papain treatment, which might be the results of a secondary response. In order to evaluate the functions of different signaling pathways in allergen-induced IL-25 and TSLP gene expression, we employed pathway-specific inhibitors. IL-25 and TSLP expression were profoundly inhibited by Erk, JNK, and p38 inhibitors (Fig. 4C, data not shown). Likewise, Asp protease also induced ErK, JNK, and p38 phosphorylation in MEF cells (data not shown).


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)

Protease allergens induce IL-25 and TSLP expression via the MAP kinase pathway. (A) Erk, JNK, and p38 MAP kinase pathways were activated via papain treatment. (B) However, boiled papain did not activate the Erk or p38 MAP kinase pathways. (C) The induction of IL-25 and TSLP of MEF cells by papain treatment is inhibited by MAP kinase inhibition. (D) The IL-25 gene expression of MyD88& TIRA-/- MEF after papain treatment is similar to that of wild type MEF. Protease allergen-induced IL-25 expression was not mediated via the MyD88 or TIRAP pathways. I-pI3K, inhibitor of pI3 kinase (LY294002); I-Erk, inhibitor of Erk MAPK (PD98059); I-p38, Inhibitor of p38 MAPK (SB203580); I-JNK, Inhibitor of JNK MAPK (JNK inhibitor II) (*P<0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Protease allergens induce IL-25 and TSLP expression via the MAP kinase pathway. (A) Erk, JNK, and p38 MAP kinase pathways were activated via papain treatment. (B) However, boiled papain did not activate the Erk or p38 MAP kinase pathways. (C) The induction of IL-25 and TSLP of MEF cells by papain treatment is inhibited by MAP kinase inhibition. (D) The IL-25 gene expression of MyD88& TIRA-/- MEF after papain treatment is similar to that of wild type MEF. Protease allergen-induced IL-25 expression was not mediated via the MyD88 or TIRAP pathways. I-pI3K, inhibitor of pI3 kinase (LY294002); I-Erk, inhibitor of Erk MAPK (PD98059); I-p38, Inhibitor of p38 MAPK (SB203580); I-JNK, Inhibitor of JNK MAPK (JNK inhibitor II) (*P<0.05).
Mentions: In an effort to address the intracellular mechanism that regulates IL-25 and TSLP expression upon stimulation with protease allergens, we evaluated the activation of intracellular MAPK and NF-κB. Papain induced the phosphorylation of ERK, JNK, and p38 MAPK in MEF cells within as short a time as 15 min (Fig. 4A). Boiled papain marginally induced p-JNK with delayed kinetics, and failed to induce the phosphorylation (Fig. 4B). On the other hand, the levels of IκBα were reduced 2 hr after papain treatment, which might be the results of a secondary response. In order to evaluate the functions of different signaling pathways in allergen-induced IL-25 and TSLP gene expression, we employed pathway-specific inhibitors. IL-25 and TSLP expression were profoundly inhibited by Erk, JNK, and p38 inhibitors (Fig. 4C, data not shown). Likewise, Asp protease also induced ErK, JNK, and p38 phosphorylation in MEF cells (data not shown).

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