Leukotriene E₄ induces MUC5AC release from human airway epithelial NCI-H292 cells

抄録

Background: Hypersecretion of mucin in the airway epithelium is an important feature of allergic airway diseases. Of the 3 cysteinyl leukotrienes (CysLTs; LTC₄ LTD₄ and LTE₄), only LTE₄ is sufficiently stable to be detectable in extracellular fluids. However, LTE₄ has received little attention because it binds poorly to the CysLT₁ and CysLT₂ receptors; therefore, little is known about the effects of LTE₄ on mucous secretion. Recently, studies have focused on the P2Y₁₂ receptor as a potential receptor for LTE₄, because this re- ceptor is required for LTE₄-mediated pulmonary inflammation. In our previous study, we confirmed the expression of P2Y₁₂ receptor in human airway epithelial cells. To clarify the roles of LTE₄ in airway epithelial cells, we investigated mucus secretion by LTE₄ in vitro.
Methods: Confluent NCI-H292 cells were stimulated with LTE₄ (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 P2Y₁₂ receptor protein. LTE₄ 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 LTE₄-induced release of MUC5AC protein. MRS2935, a P2Y₁₂ receptor antagonist, partially inhibited the LTE₄-induced release of MUC5AC protein in the airway. In contrast, MK571, a CysLT₁ receptor antagonist, did not affect the release of MUC5AC protein elicited by LTE₄.
Conclusions: These results suggest that LTE₄ may play some important roles in allergic mucus secretion partially via activation of P2Y₁₂ receptor.