TNF GENE EXPRESSION IN MONOCYTES OF LOW AND HIGH RESPONDER INDIVIDUALS

Individuals with a consistently lower immune response may be more susceptible to infection but less prone to autoimmune disease or severe sepsis. The molecular mechanisms determining the low responder status are, however, unclear. We have screened 60 male donors for tumour necrosis factor (TNF) prot...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 1997-03, Vol.9 (3), p.206-211
Main Authors: Schraut, Winfried, Wendelgass, Petra, Calzada-Wack, Julia C., Frankenberger, Marion, Ziegler-Heitbrock, H.W.Löms
Format: Article
Language:English
Subjects:
Blotting, Northern
Cycloheximide - pharmacology
Dactinomycin - pharmacology
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
Humans
Immunity
Interleukin-6 - genetics
Interleukin-6 - metabolism
Lipopolysaccharides - pharmacology
LPS
Male
Monocyte
Monocytes - drug effects
Monocytes - metabolism
Nucleic Acid Synthesis Inhibitors - pharmacology
Protein Synthesis Inhibitors - pharmacology
RNA, Messenger - metabolism
Signal Transduction
TNF
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
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Summary:Individuals with a consistently lower immune response may be more susceptible to infection but less prone to autoimmune disease or severe sepsis. The molecular mechanisms determining the low responder status are, however, unclear. We have screened 60 male donors for tumour necrosis factor (TNF) protein levels after stimulation of monocytes with lipopolysaccharide (LPS). Among these we identified three donors each that consistently had a level of less than 20% (low responders; LR) or of more than 80% (high responders; HR) of the maximum response seen in this population. Northern blot analysis of TNF mRNA after LPS stimulation revealed lower transcript levels in LR. Half life determination after actinomycin D blockade showed a similar decay rate for LR and HR and after blockade of degradation by cycloheximide treatment mRNA levels increased but LR remained lower compared to HR. These data indicate that the lower TNF mRNA levels in LR are not due to a more rapid mRNA degradation but rather a result of lower transcription. Transcripts for interleukin 6 (IL-6) were also low in LPS-stimulated monocytes of LR. Because expression of the LPS receptor CD14 was similar in LR and HR monocytes, our data suggest that differences in signal transduction account for the LR and HR phenotype.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.1996.0155