Effects of Repeated Antigen Exposure on the Expression of Enzymes Associated with Sphingosine-1-Phosphate Turnover

Increasing evidence suggests that sphingosine-1-phosphate (S1P) is involved in the pathogenesis of allergic bronchial asthma. In the present study, the changes in the expression levels of enzymes associated with S1P turnover were determined in a mouse model of allergic bronchial asthma. Male BALB/c mice were actively sensitized with ovalbumin antigen, and were repeatedly challenged with aerosolized antigen. Twenty-four hours after the last antigen, total RNAs were extracted from lungs. The RT-PCR analyses revealed that mRNAs for the S1P-producing enzymes, sphingosine kinase 1 (SphK1) and SphK2, and for the S1P-breakdown enzymes, S1P phosphatase 1 (S1PP1), S1PP2, S1P lyase, and lipid phosphate phosphatase 1a, were expressed in the lungs of mice. Among them, the mRNA levels of SphK2 and S1PP1 were significantly increased in the lungs of the repeatedly antigen-challenged mice. It is thus possible that the S1P turnover is increased in the airways of allergic bronchial asthma.