The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice

• DE and/or FB1 treatment unaltered expression of Nos2 mRNA.
• FB1 suppressed ceramide production Sphk1, SP-A and SP-D mRNA expressions.
• Pulmonary ceramide and Sphk1 was reflected as biomarkers for DE exposure.
• Ceramide was contributed to the DE-induced early stage of airway affection.
• Ceramide was a potential pulmonary therapeutic target in the low-level DE exposure.

Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6 J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1 mg/m3), FB1 (6.75 mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP-A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE-induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure.