Lipopolysaccharide-stimulated or granulocyte-macrophage colony-stimulating factor-stimulated monocytes rapidly express biologically active IL-15 on their cell surface independent of new protein synthesis.

Although IL-15 shares many of the biological activities of IL-2, IL-2 expression is primarily under transcriptional regulation, while the mechanisms involved in the regulation of IL-15 are complex and not completely understood. In the current study, we found that CD14(+) monocytes constitutively exhibit both IL-15 mRNA and protein. IL-15 protein was found stored intracellularly and stimulation of CD14(+) monocytes with either LPS or GM-CSF resulted in mobilization of IL-15 stores to the plasma membrane. This rapidly induced surface expression was the result of a translocation of preformed stores, confirming that posttranslational regulatory stages limit IL-15, because it was not accompanied by an increase in IL-15 mRNA and occurred independent of de novo protein synthesis. After fixation, activated monocytes, but not resting monocytes, were found to support T cell proliferation, and this effect was abrogated by the addition of an IL-15-neutralizing Ab. The presence of preformed IL-15 stores and the ability of stimulated monocytes to mobilize these stores to their surface in an active form is a novel mechanism of regulation for IL-15.

Urethane suppresses rat lung inducible cyclooxygenase and nitric oxide synthase mRNA levels.

OBJECTIVE AND DESIGN: The purpose of the present study was to evaluate the effect of urethane, pentobarbital sodium and ketamine-xylazine anesthesia upon constitutive and inducible cyclooxygenase (COX-1; COX-2) and nitric oxide synthase (eNOS; iNOS) mRNA levels in the lung. METHODS: mRNA levels were determined by the semiquantitative RT-PCR technique. TREATMENT: Urethane (1.1 g/kg ip), Pentobarbital Sodium (40 mg/kg ip), and ketamine (85 mg/kg) - xylazine (15 mg/kg, im). Non-anesthetized animals served as controls. MATERIAL: Sprague-Dawley rat lungs RESULTS: Urethane significantly decreased COX-1 and COX-2 mRNA levels to 30% of control values. This agent had no effect upon eNOS, but completely suppressed iNOS mRNA levels. Pentobarbital sodium and ketamine had no effect on the mRNA levels for COX-1 and COX-2 the lung. CONCLUSIONS: Urethane has a suppressive effect on COX and iNOS RNA message in the lung and for this reason it should be avoided as an anesthetic when lung inflammatory processes are experimentally evaluated in the rat.