Natural porcine surfactant (Curosurf) down-regulates mRNA of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha type II receptor in lipopolysaccharide-stimulated monocytes

Abstract

We have previously shown that Curosurf, a natural porcine surfactant, and its phospholipids effectively suppressed secretion of tumor necrosis factor (TNF-alpha) by resting and through lipopolysaccharide (LPS)-stimulated human monocytes. In this study the effect of Curosurf on monocyte mRNA for TNF-alpha and TNF-alpha type II-receptor (TNF-alpha-RII) were analyzed to evaluate the cellular mechanisms involved in the modulation of TNF-alpha expression. LPS-stimulated monocytes simultaneously exposed to Curosurf (500 microg/mL for 24 h) expressed approximately 70% less TNF-alpha mRNA when compared with control subjects (p < 0.05). In addition, 86% less TNF-alpha RII mRNA was found in monocytes exposed to Curosurf (p < 0.001). Decreased mRNA expression was clearly associated with significantly reduced secretion of TNF-alpha protein (Curosurf-exposed LPS-stimulated monocytes 3628 +/- 1873 pg/mL TNF, LPS-stimulated monocytes 31,376 +/- 2524 pg/mL TNF; mean +/- SEM, p < 0.001). The activation of the transcription factor nuclear factor-kappaB upon LPS stimulation is not affected by Curosurf incubation. This excludes that the decrease in mRNA and protein levels of TNF-alpha and TNF-alpha-RII is due to an inhibition of nuclear factor-kappaB activation by Curosurf. We conclude that Curosurf affects TNF-alpha release of LPS-stimulated monocytes at a pretranslational site by down-regulating both mRNA for TNF-alpha and TNF-alpha-RII, therefore acting as an anti-inflammatory agent within alveolar space.