Dexamethasone enhances P-selectin mRNA expression in hyperoxic rat lungs

Objective and Design: To test the hypothesis that glucocorticoid administra tion would diminish the lung expression of P-selectin mRNA in hyperoxia-exp osed rats. Animals: Adult male Sprague-Dawley rats were divided into 6 sepa rate groups containing 10 to 13 animals per group. Treatment: Rats were dosed with 1 mg/kg of dexamethasone or vehicle only, i p. Immediately after dosing, animals were placed in > 95 % oxygen. Some ani mals were maintained in room air and are presented as 0 h of exposure to hy peroxia. Another group of animals was dosed with 10 mg/kg lipopolysaccharid e (LPS) ip immediately after dosing with either dexamethasone or vehicle as above. Methods: At 24 or 48 h, lung samples were obtained, and lung weight to body weight ratios calculated. In the LPS studies, samples were obtained 4 h af ter LPS dosing. In a subset of animals, lung sections were hybridized for P -selectin mRNA. All data except for hybridizations were analyzed with three -way ANOVA, with subsequent post-hoc testing. P-selectin hybridizations wer e quantified by counting the number of positive vessels per high-powered fi eld, and subsequently analyzed by unpaired Student's t-test. Immunohistoche mical analyses for P-selectin expression were also performed to determine w hether changes in P-selectin mRNA were associated with differences in prote in expression. All data are expressed as means +/- SEM. Results: Rats dosed with dexamethasone had higher lung/body weight ratios a fter 24 and 48 h of exposure to hyperoxia than did similarly exposed rats d osed only with vehicle (at 48 h, 0.87 +/- 0.04 versus 0.65 +/- 0.06, respec tively, P<0.05). The higher ratios in hyperoxic animals dosed with dexameth asone were associated with much higher levels of lung expression for P-sele ctin mRNA than was observed in similarly exposed rats dosed with vehicle al one (at 48 h, 3.93 +/- 1.02, versus 0.20 +/- 0.06, respectively, P<0.01). I n contrast dexamethasone dosing lead to lower lung P-selectin mRNA expressi on in animals exposed to LPS (1.23 +/- 1.08 in dexamethasone dosed animals versus 6.80 +/- 0.92 in vehicle only dosed animals). Consistent with the mR NA data, P-selectin immunoreactivity increased as a function of hyperoxia-e xposure time in animals dosed with dexamethasone, while immunoreactivity de creased as a function of hyperoxia-exposure time in animals dosed with vehi cle only. Conclusions: Increased P-selectin mRNA combined with increased P-selectin p rotein expression in animals exposed to hyperoxia and dosed with dexamethas one suggests that enhanced expression of P-selectin may contribute to the g reater lung injury and inflammation caused by hyperoxia in rats treated wit h dexamethasone.