The protooncogene c-fos is transcriptionally active in normal human granulocytes

Heidorn, K; Kreipe, H; Radzun, H. J.; Muller, R; Mr, Parwaresch

doi:10.1182/blood.v70.2.456.bloodjournal702456

Cited by 4 publications

(4 citation statements)

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“…A minor band of about 3.4 kb, suggested to be a precursor molecule [1,2], was also evident, but only after overexposure of the autoradiogram. The sizes of jun B and jun D transcripts were about 2.1 and 2.0 kb respectively, as already reported [10,21]. The level of expression found for c-jun mRNA was comparable with that found for the 2.2 kb c-fos mRNA ([9]; F. Mollinedo & J. R. Naranjo, unpublished work).…”

Section: Resultssupporting

confidence: 85%

“…Two other c-jun-related cDNAs have been isolated (jun B and jun D), whose encoded proteins show extensive amino acid sequence identity with c-Jun/AP-and are able to form nuclear complexes with c-Fos or Fos-related proteins [7,8]. It has been found that human granulocytes express constitutively high levels of c-fos mRNA [9][10][11][12], which were increased upon cell activation by distinct stimuli [9][10][11][12][13]. Thus it was of importance to examine the expression of the jun family genes in granulocytes.…”

Section: Introductionmentioning

confidence: 99%

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Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes

Mollinedo

Vaquerizo

Naranjo

1991

Biochemical Journal

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We have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun, jun B and jun D mRNA. Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13-acetate (PMA), the levels of c-jun, jun B and jun D transcripts were increased. The three jun genes showed a similar time course in their induction by PMA, maximal mRNA levels being reached after 60 min of induction. These results suggest that expression of c-jun, jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes

Mollinedo

Vaquerizo

Naranjo

1991

Biochemical Journal

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“…Given the evidence that sgk is an immediate-early gene, its time-course of expression was compared to c-fos, another immediate-early gene known to be up-regulated by GM-CSF in granulocytes. Freshly isolated human peripheral blood granulocytes contain appreciable levels of c-fos mRNA [17,60,61]. Various stimulators of granulocyte function, including GM-CSF, can further increase c-fos levels [17,62].…”

Section: Resultsmentioning

confidence: 99%

Expression of serum- and glucocorticoid-regulated kinase (sgk) mRNA is up-regulated by GM-CSF and other proinflammatory mediators in human granulocytes

Cowling

Birnboim

2000

Journal of Leukocyte Biology

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Stimulation of human peripheral blood granulocytes with the proinflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), increases incorporation of [ 3 H]uridine into RNA. We investigated the nature of the RNA synthesized under these conditions. Using transcription inhibitors, gel electrophoresis, and high-salt precipitation, it was concluded that as much as 90% of this radiolabeled RNA represents polymerase II transcripts. Differential display reverse transcription-polymerase chain reaction was used to identify and clone GM-CSF-responsive mRNAs. Serum-and glucocorticoid-regulated kinase (sgk) mRNA was identified that could be up-regulated 10-to 20-fold by Ն0.1 ng/mL recombinant human GM-CSF. The 2.6-kb sgk mRNA was induced rapidly (within 30 min) by GM-CSF and remained at high levels for at least 12 h. Up-regulation was blocked completely by the transcription inhibitor, actinomycin D, but not by the translation inhibitor, cycloheximide, nor by the tyrosine kinase inhibitor, genistein. Up-regulation did not appear to be caused by enhanced mRNA stability. Other inflammatory mediators could also increase sgk mRNA levels (GM-CSF GG lipopolysaccharide G fMLP ‫؍‬ tumor necrosis factor ␣). The function of sgk in granulocytes remains unknown. J. Leukoc. Biol. 67: 240-248; 2000.

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“…In PMN performing 'frustrated' phagocytosis we did not find significant differences in the NF-κB pathway, however, FOS and JUN (the proteins c-fos and c-jun form the transcriptional regulator AP-1) were both increasingly expressed. PMN have been reported to constitutively express family members of FOS and JUN on transcriptional as well as c-fos and c-jun on translational level [32][33][34][35] with the steady state level of their RNA transcripts being rapidly up-regulated in response to several stimuli [36,37]. However, neither the proteins c-jun and c-fos nor the protein AP-1 has been shown to be up-regulated in PMN after exposure to diverse stimuli as indicated by our results and as reported by others [34,35].…”

Section: Discussionmentioning

confidence: 99%

In vitro – transcriptional response of polymorphonuclear leukocytes following contact with different antigens

Hochegger

Perco

Enrich

et al. 2007

Eur J Clin Investigation

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Background Human polymorphonuclear neutrophils (PMN) are activated and undergo apoptosis if brought into contact with cuprophane haemodialysis membranes, a phenomenon not observed if more 'biocompatible' polysulfone dialysers are used. It remains yet to be defined if this differential response is due to mechanisms regulated on a transcriptional or protein level. Furthermore, it is not clear if the contact of PMN with membranes ('frustrated' phagocytosis) activates the same response as phagocytosis of bacteria (complete phagocytosis). Materials and methods We performed a genome-wide differential gene expression study using cDNA microarrays to analyse the impact of different dialysis fibres on the transcriptional response of PMN of human healthy volunteers. These results were compared to transcriptional response of PMN during phagocytosis of Escherichia coli. Results We did not detect significant differences in gene expression between PMN stimulated with cuprophane or pulysulfone. Compared to unstimulated PMN the 'frustrated' phagocytosis of either dialysis membrane resulted in increased expression of 50 genes, with a marked up-regulation of FOS - and JUN - transcripts, but with only little activation of immune response genes, and virtually no activation of apoptosis related RNA transcripts. In contrast, phagocytosis of E.coli was associated with a striking up-regulation of 88 genes, most of them involved in pro- and antiapoptotic pathways, immune response and activation of nuclear factor kappa B and inhibitor of NF-kappa B. Conclusions Our results suggest that the response of PMN to artificial surfaces is not controlled on transcriptional level. Complete and 'frustrated' phagocytosis activate markedly distinct transcriptional regulatory pathways in PMN.

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The protooncogene c-fos is transcriptionally active in normal human granulocytes

Cited by 4 publications

References 0 publications

Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes

Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes

Expression of serum- and glucocorticoid-regulated kinase (sgk) mRNA is up-regulated by GM-CSF and other proinflammatory mediators in human granulocytes

In vitro – transcriptional response of polymorphonuclear leukocytes following contact with different antigens

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