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Role of Allergen Source-Derived Proteases in Sensitization via Airway Epithelial Cells.

Matsumura Y - J Allergy (Cairo) (2012)

Bottom Line: Protease activity is a characteristic common to many allergens.These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism.Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Akishima Hospital, 1260 Nakagami-Cho, Akishima-Shi, Tokyo 196-0022, Japan.

ABSTRACT
Protease activity is a characteristic common to many allergens. Allergen source-derived proteases interact with lung epithelial cells, which are now thought to play vital roles in both innate and adaptive immune responses. Allergen source-derived proteases act on airway epithelial cells to induce disruption of the tight junctions between epithelial cells, activation of protease-activated receptor-2, and the production of thymic stromal lymphopoietin. These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism. Furthermore, they cleave regulatory cell surface molecules involved in allergic reactions. Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

No MeSH data available.


Related in: MedlinePlus

Allergen source-derived proteases compromise epithelial barrier function by degrading TJ proteins, facilitating allergen accessibility to DCs. Enzymatically active allergens can activate PAR to induce TSLP. TSLP induces immediate innate immune functions in DCs, leading to recruitment of inflammatory cells. TSLP triggers the maturation of DCs, so they migrate to mediastinal lymph nodes. Induction of DCs to upregulate OX40L by TSLP promotes Th2 responses. PAR also upregulates production of MMP-9, which degrades tight junction proteins. Thus, impairment of airway epithelial barrier function and activation of epithelial cells are involved in the pathogenesis of inflammation mediated by allergen source-derived proteases.
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fig1: Allergen source-derived proteases compromise epithelial barrier function by degrading TJ proteins, facilitating allergen accessibility to DCs. Enzymatically active allergens can activate PAR to induce TSLP. TSLP induces immediate innate immune functions in DCs, leading to recruitment of inflammatory cells. TSLP triggers the maturation of DCs, so they migrate to mediastinal lymph nodes. Induction of DCs to upregulate OX40L by TSLP promotes Th2 responses. PAR also upregulates production of MMP-9, which degrades tight junction proteins. Thus, impairment of airway epithelial barrier function and activation of epithelial cells are involved in the pathogenesis of inflammation mediated by allergen source-derived proteases.

Mentions: IL-25 and TSLP perform important functions in the initiation of allergic responses [120–122]. TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases, and PAR-2 is involved in this process. A recent study demonstrated upregulation of IL-25 and TSLP mRNA in pulmonary epithelial cells after protease allergen treatment in vivo and in vitro, and that the induction of IL-25 and TSLP occurs via the intracellular ERK and p38 MAP kinase pathways [123]. TSLP induces the innate immune functions of DCs, leading to chemokine-driven recruitment of Th2 cells to the airway, and these cells then produce Th2 type cytokines. TSLP also triggers the maturation of DCs and their migration to mediastinal lymph nodes, again skewing the T-cell distribution in favor of inflammatory Th2 cells producing IL-4, IL-5, IL-13, and TNF-α. These processes involve interactions between costimulatory molecules, such as OX40 (CD134) in the membranes of naïve T cells and OX40L (CD134L) in the membranes of DCs [124, 125]. TSLP was reported to be induced in the airway epithelial cell line BEAS-2B by exposure to Alternaria proteases [126] (see Figure 1).


Role of Allergen Source-Derived Proteases in Sensitization via Airway Epithelial Cells.

Matsumura Y - J Allergy (Cairo) (2012)

Allergen source-derived proteases compromise epithelial barrier function by degrading TJ proteins, facilitating allergen accessibility to DCs. Enzymatically active allergens can activate PAR to induce TSLP. TSLP induces immediate innate immune functions in DCs, leading to recruitment of inflammatory cells. TSLP triggers the maturation of DCs, so they migrate to mediastinal lymph nodes. Induction of DCs to upregulate OX40L by TSLP promotes Th2 responses. PAR also upregulates production of MMP-9, which degrades tight junction proteins. Thus, impairment of airway epithelial barrier function and activation of epithelial cells are involved in the pathogenesis of inflammation mediated by allergen source-derived proteases.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303585&req=5

fig1: Allergen source-derived proteases compromise epithelial barrier function by degrading TJ proteins, facilitating allergen accessibility to DCs. Enzymatically active allergens can activate PAR to induce TSLP. TSLP induces immediate innate immune functions in DCs, leading to recruitment of inflammatory cells. TSLP triggers the maturation of DCs, so they migrate to mediastinal lymph nodes. Induction of DCs to upregulate OX40L by TSLP promotes Th2 responses. PAR also upregulates production of MMP-9, which degrades tight junction proteins. Thus, impairment of airway epithelial barrier function and activation of epithelial cells are involved in the pathogenesis of inflammation mediated by allergen source-derived proteases.
Mentions: IL-25 and TSLP perform important functions in the initiation of allergic responses [120–122]. TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases, and PAR-2 is involved in this process. A recent study demonstrated upregulation of IL-25 and TSLP mRNA in pulmonary epithelial cells after protease allergen treatment in vivo and in vitro, and that the induction of IL-25 and TSLP occurs via the intracellular ERK and p38 MAP kinase pathways [123]. TSLP induces the innate immune functions of DCs, leading to chemokine-driven recruitment of Th2 cells to the airway, and these cells then produce Th2 type cytokines. TSLP also triggers the maturation of DCs and their migration to mediastinal lymph nodes, again skewing the T-cell distribution in favor of inflammatory Th2 cells producing IL-4, IL-5, IL-13, and TNF-α. These processes involve interactions between costimulatory molecules, such as OX40 (CD134) in the membranes of naïve T cells and OX40L (CD134L) in the membranes of DCs [124, 125]. TSLP was reported to be induced in the airway epithelial cell line BEAS-2B by exposure to Alternaria proteases [126] (see Figure 1).

Bottom Line: Protease activity is a characteristic common to many allergens.These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism.Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Akishima Hospital, 1260 Nakagami-Cho, Akishima-Shi, Tokyo 196-0022, Japan.

ABSTRACT
Protease activity is a characteristic common to many allergens. Allergen source-derived proteases interact with lung epithelial cells, which are now thought to play vital roles in both innate and adaptive immune responses. Allergen source-derived proteases act on airway epithelial cells to induce disruption of the tight junctions between epithelial cells, activation of protease-activated receptor-2, and the production of thymic stromal lymphopoietin. These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism. Furthermore, they cleave regulatory cell surface molecules involved in allergic reactions. Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

No MeSH data available.


Related in: MedlinePlus