Contrasting effects of long-term treatment with IFN-gamma in endothelial cells: increase in IL-6 secretion versus decrease in IL-8 secretion, NF-kappa B, and AP-1 activation.
The benefit of neutrophil exclusion from type 1 T helper cell (TH1) inflammatory processes was demonstrated in clinical studies. Increased recruitment of lymphocytes and monocytes to endothelium and impaired recruitment of polymorphonuclear neutrophils (PMNs) following interferon-gamma (IFN-gamma) treatment were described. The present study demonstrates that a 24 h treatment with IFN-gamma increases interleukin (IL)-6 release but reduces IL-8 secretion of both untreated and of tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells (ECs), favoring the attraction of lymphocytes but not of neutrophils. Alteration of cytokine release was accompanied by reduced basal and TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) activity. However, IFN-gamma application neither altered gene expression of both TNF-alpha receptors (p55 and p75) nor cellular density of TNF-alpha receptor-2 (p75). Therefore, immune-modulatory action of IFN-gamma seems to be mediated by signal transduction molecules.
Borgmann
S
S
Institute of Medical Microbiology, Eberhard-Karl-University of Tübingen, Germany. Stefan.Borgmann@med.uni-tuebingen.de
Bayer
A
A
König
W
W
Ambrosch
A
A
Kraus
J
J
D015703:Antigens, CD / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism*
D015703:Antigens, CD; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D018808:Transcription Factor AP-1; D007371:Interferon-gamma