Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that the synthetic surfactant Exosurf and a modified natural surfactant, Survanta, both down-regulated endotoxin-stimulated production of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) in human alveolar macrophages. To further characterize the source of the inhibitory effect of surfactant, the three individual components of Exosurf were evaluated. Dipalmitoylphosphatidylcholine had no effect on endotoxin-stimulated cytokine secretion. Cetyl alcohol (spreading agent) compromised macrophage function as measured by adherence. However, at concentrations equivalent to those found in the complete surfactant (Exosurf) preparation, tyloxapol (nonionic dispersing agent) was inhibitory in a dose-dependent manner. The viability of alveolar macrophages as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide cleavage assay was not affected by incubation in Exosurf or any of its individual components. Cytokine secretion and mRNA levels of endotoxin-stimulated alveolar macrophages were decreased by tyloxapol. These data suggest that tyloxapol alone, like Exosurf, has an inhibitory effect on cytokine production which may be pretranslationally mediated.
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PMID:Regulation of human alveolar macrophage inflammatory cytokines by tyloxapol: a component of the synthetic surfactant Exosurf. 758 28

In addition to biophysical properties, pulmonary surfactant has immunomodulatory activity. We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages. In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line. Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line, we used this cell line to investigate whether surfactant affected transcriptional mechanisms. Specifically, we examined nuclear factor-kappa B (NF-kappa B) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF, IL-1, and IL-6. Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B. The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays. These results are the first to suggest that surfactant's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation.
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PMID:Surfactant suppresses NF-kappa B activation in human monocytic cells. 860 Sep 42