Abstract
Purpose:
Interleukin(IL)-33 as well as Thymic stromal lymphopoietin (TSLP) and IL-25 induce Th2 cytokine production by various types of cells, suspecting to involvement of these cytokines in development of allergic disorders. Supportively, we reported that IL-33 expression was increased in conjunctival epithelium of the giant papillae from patients with chronic allergic conjunctivitis (IOVS. 50:4646-52, 2009). In association with this, in the present study, we investigated the roles of IL-33 IL-25 and TSLP in papain-induced conjunctivitis using IL-33-deficient (IL-33-/-), IL-25-/- and TSLP receptor (TSLPR) -/- mice.
Methods:
Papain-induced conjunctivitis in mice was established as below; C57BL/6 mice were had contact lenses (2mm diameter), which were soaked in papain solution for a right eye or in heat-inactivated papain solution as controls for a left eye. After fitting contact lenses, the eyelids were sutured. Two days later, the contact lenses were replaced by a new papain-soaked or control lens. Four days after first papain installation, histological analysis and gene expression analysis by realtime PCR were carried out in the resected conjunctival samples.
Results:
The number of eosinophils in conjunctiva and the expression levels of IL-4 and IL-13 mRNA were significantly reduced in IL-33-/- and TSLPR-/-, but not IL-25-/-, mice in comparison with wild-type mice during papain-induced conjunctivitis (IL-33-/- mice: 10.4 ± 5.2 P< 0.05, TSLPR-/- mice: 22.5 ± 4.5 P< 0.05, IL-25-/- mice: 32.9 ± 4.5 P> 0.05, versus wild-type mice: 40.6 ± 9.8, mean number of eosinophil ± SD per slides, n = 10, by Mann-Whitney’s U test).
Conclusions:
IL-33 and TSLP, but not IL-25, produced by conjunctiva epithelial cells are crucial for the development of papain-induced allergic conjunctivitis. Our findings suggest that neutralization of IL-33 and TSLP may provide a potential target for novel therapeutic treatment for allergic conjunctivitis.
Keywords: 474 conjunctiva •
475 conjunctivitis •
553 immune tolerance/privilege