scholarly journals Lipopolysaccharides prime whole human blood and isolated neutrophils for the increased synthesis of 5-lipoxygenase products by enhancing arachidonic acid availability: involvement of the CD14 antigen.

1993 ◽  
Vol 178 (4) ◽  
pp. 1347-1355 ◽  
Author(s):  
M E Surette ◽  
R Palmantier ◽  
J Gosselin ◽  
P Borgeat
Keyword(s):  
Arachidonic Acid ◽  
Mononuclear Cells ◽  
Leukotriene B4 ◽  
Eicosatetraenoic Acid ◽  
Tnf Alpha ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Priming Activity

Stimulation of heparinized blood with 1 microM formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in the formation of < 30 pmol/ml plasma of 5-lipoxygenase (5-LO) products. The preincubation of blood with 1 microgram/ml of lipopolysaccharide (LPS) (Escherichia coli 0111-B4) for 30 min before stimulation with FMLP resulted in the accumulation of 250-300 pmol of 5-LO products per ml plasma. The major products detected were leukotriene B4 and (5S)-hydroxy-6,8,11,14-eicosatetraenoic acid which were produced in equivalent amounts. The priming activity was detectable with as little as 1-10 ng LPS per ml blood and was optimal using 1-10 micrograms LPS/ml blood. The priming for 5-LO product synthesis was optimal after 20-30 min of preincubation with LPS and declined at preincubation times > 30 min. The priming effect of LPS was also observed using the complement fragment C5a or interleukin 8 as agonists. Polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells accounted for 80 and 20% of the synthesis of 5-LO products, respectively. The ability of LPS to prime isolated PMN was dependent on the presence of plasma and was inhibited by the anti-CD14 antibody IOM2, indicating a CD14-dependent priming mechanism. The priming of whole blood with tumor necrosis factor alpha (TNF-alpha) and LPS was additive and the presence of mononuclear cells did not enhance the ability of LPS to prime PMN, indicating that the priming activity of LPS is independent of LPS-induced TNF-alpha synthesis. The mechanism by which LPS enhance 5-LO product synthesis in PMN was investigated. Treatment of PMN with LPS strongly enhanced the release of arachidonic acid after stimulation with FMLP. The release of arachidonic acid was optimal 2-3 min after stimulation with FMLP, attaining levels 5-15-fold greater than those observed in unprimed cells stimulated with FMLP. These results demonstrate that LPS dramatically increases the ability of blood to generate 5-LO products, and support the putative role of leukotrienes in pathological states involving LPS.

The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1

1993 ◽  
Vol 13 (7) ◽  
pp. 4284-4290
Author(s):  
M A Brach ◽  
H J Gruss ◽  
C Sott ◽  
F Herrmann
Keyword(s):  
Tumor Necrosis ◽  
Growth Stimulation ◽  
Myelogenous Leukemia ◽  
Tnf Alpha ◽  
Mitogenic Response ◽  
Necrosis Factor Alpha ◽  
Acute Myelogenous ◽  
Factor Alpha ◽  
Necrosis Factor

In the present study, we addressed the role of the c-jun proto-oncogene in the mitogenic response of human fibroblasts and primary acute myelogenous leukemia blasts to tumor necrosis factor alpha (TNF-alpha). Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun, resulting in accumulation of c-jun mRNA and protein expression. In order to elucidate the role of c-Jun/AP-1 in TNF-mediated growth stimulation, the antisense (AS) technique was used. Uptake studies of oligonucleotides were performed with fibroblasts, demonstrating that incorporation of oligomers was maximal at 4 h. Oligodeoxynucleotides remained stable in these cells for up to 24 h. Treatment of fibroblasts with the AS oligonucleotide resulted in intracellular duplex formation followed by an efficient translation blockade of c-Jun/AP-1. In contrast, sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c-Jun/AP-1, suggesting specific elimination of c-Jun/AP-1 by the AS oligomer. Fibroblasts cultured in the presence of the AS oligonucleotide but not those cultured in the presence of the S or NS oligonucleotide failed to respond proliferatively to TNF-alpha. These findings could be confirmed by experiments with primary acute myelogenous leukemia blasts, which also demonstrated that TNF-induced growth stimulation required c-Jun/AP-1 function. Taken together, our results indicate that activation of c-Jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF, which leads to a proliferative response of its target cells.

scholarly journals Cytokine Production in Cell Culture by Peripheral Blood Mononuclear Cells from Immunocompetent Hosts

1998 ◽  
Vol 5 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Rohit K. Katial ◽  
Doris Sachanandani ◽  
Carolyn Pinney ◽  
Michael M. Lieberman
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Pokeweed Mitogen ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Blood Mononuclear Cells ◽  
Factor Alpha

ABSTRACT The production of interleukin 2 (IL-2) gamma interferon, IL-4, tumor necrosis factor alpha (TNF-α), TNF-β, IL-5, and IL-10 in vitro by peripheral blood mononuclear cells cultured from healthy immunocompetent subjects after mitogen stimulation was determined. The mitogens used were concanavalin A, phytohemagglutinin, pokeweed mitogen, and Staphylococcus aureus Cowen. The results obtained provide a normal range for the production of these cytokines under specified conditions in vitro.

scholarly journals The Treponema denticola Surface Protease Dentilisin Degrades Interleukin-1β (IL-1β), IL-6, and Tumor Necrosis Factor Alpha

2006 ◽  
Vol 74 (4) ◽  
pp. 2462-2467 ◽  
Author(s):  
Meguru Miyamoto ◽  
Kazuyuki Ishihara ◽  
Katsuji Okuda
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Interleukin 1Β ◽  
Treponema Denticola ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Dentilisin is a major surface protease and virulence factor of the bacterium Treponema denticola. In this study, we found that T. denticola reduced inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha, in peripheral blood mononuclear cells through degradation by dentilisin.

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