Role of MIF and glutathione, in association with fetal ovine globin chain (Hbgamma) and LPS, in induction of TNFalpha from cells of young and aged mice, and PBL from healthy human populations

Previous reports from our group have established that the fetal ovine gamma globin chain (Hbgamma) and LPS can synergize in the induction of pro-inflammatory cytokines, especially TNFalpha, from mouse and human leukocytes. A fetal sheep liver extract (FSLE) which was observed to have marked immunore...

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Published in:Immunology letters 2006-06, Vol.105 (2), p.140-149
Main Authors: Gorczynski, R M, Alexander, C, Bessler, W, Brandenburg, K, Fournier, K, Hoffmann, P, Mach, J P, Mueller, S, Rietschel, E Th, Terzioglu, E, Ulmer, A J, Waelli, Th, Zahringer, U, Khatri, I
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Cell Extracts - chemistry
Cell Extracts - pharmacology
Cell Polarity
Cells, Cultured
Fetal Blood - metabolism
Glutathione - pharmacology
Health
Heme - metabolism
Hemoglobins - isolation & purification
Hemoglobins - metabolism
Humans
Leukocytes - drug effects
Leukocytes - metabolism
Lipopolysaccharides - pharmacology
Liver - cytology
Liver - metabolism
Macrophage Migration-Inhibitory Factors - immunology
Macrophage Migration-Inhibitory Factors - pharmacology
Mice
Mice, Inbred C57BL
Recombinant Proteins - immunology
Recombinant Proteins - pharmacology
Sheep
Tumor Necrosis Factor-alpha - biosynthesis
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Summary:Previous reports from our group have established that the fetal ovine gamma globin chain (Hbgamma) and LPS can synergize in the induction of pro-inflammatory cytokines, especially TNFalpha, from mouse and human leukocytes. A fetal sheep liver extract (FSLE) which was observed to have marked immunoregulatory properties in vivo and in vitro had independently been observed to contain significant amounts of each of these molecules. However, the biological activity of this extract (hereafter FSLE) was not explained solely by its content of Hbgamma and LPS, and independent analysis confirmed also the presence of migration inhibitory factor, MIF, and glutathione in FSLE. We have investigated whether MIF and the cellular anti-oxidant glutathione can further synergize with Hbgamma and LPS in TNFalpha induction from human cells in vitro, and mouse cells activated in vivo/in vitro. Our data show that indeed there is evidence for such a synergy. Treatment or mouse cells with FSLE produced an enhanced TNFalpha production which could be inhibited independently both by anti-Hbgamma and by anti-MIF, and optimally by a combination of these reagents.
ISSN:0165-2478