Background: Hypersecretion of mucin in the airway epithelium is an important feature of allergic airway diseases. Of the 3 cysteinyl leukotrienes (CysLTs; LTC
4 LTD
4 and LTE
4), only LTE
4 is sufficiently stable to be detectable in extracellular fluids. However, LTE
4 has received little attention because it binds poorly to the CysLT
1 and CysLT
2 receptors; therefore, little is known about the effects of LTE
4 on mucous secretion. Recently, studies have focused on the P2Y
12 receptor as a potential receptor for LTE
4, because this re- ceptor is required for LTE
4-mediated pulmonary inflammation. In our previous study, we confirmed the expression of P2Y
12 receptor in human airway epithelial cells. To clarify the roles of LTE
4 in airway epithelial cells, we investigated mucus secretion by LTE
4 in vitro.
Methods: Confluent NCI-H292 cells were stimulated with LTE
4 (0.01-1 μM) for 24 h. The release and production of MUC5AC protein, a gel-forming mucin, were evaluated with an enzyme-linked immu- nosorbent assay.
Results: Western blot analysis revealed that NCI-H292 cells expressed P2Y
12 receptor protein. LTE
4 significantly induced the release of MUC5AC mucin in a dose-dependent manner. Th2 cytokines such as IL-4 (10 ng/mL) and IL-13 (10 ng/mL) accelerated the LTE
4-induced release of MUC5AC protein. MRS2935, a P2Y
12 receptor antagonist, partially inhibited the LTE
4-induced release of MUC5AC protein in the airway. In contrast, MK571, a CysLT
1 receptor antagonist, did not affect the release of MUC5AC protein elicited by LTE
4.
Conclusions: These results suggest that LTE
4 may play some important roles in allergic mucus secretion partially via activation of P2Y
12 receptor.
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