Molecular mechanisms in down-regulation of tumor necrosis factor expression

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.24.9563· OSTI ID:5029604

Haas, J G; Riethmueller, G; Ziegler-Heitbrock, H W.L. ^[1]; Baeuerle, P A ^[2]

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1. Univ. of Munich, (West Germany)
2. Univ. of Munich, Martinsried (West Germany)

Excessive production of tumor necrosis factor (TNF) after stimulation by lipopolysaccharide (LPS) may result in fever, intravascular coagulation, and lethal shock. An efficient way of preventing the excessive TNF production is desensitization of monocytes/macrophages to LPS. The authors have analyzed the molecular mechanisms involved in the induction of desensitization and the mechanisms operative in the desensitized, LPS-refractory cells by employing the human monocytic cell line Mono-Mac-6. Similar to human blood monocytes, treatment of Mono-Mac-6 cells with LPS results in a rapid and transient expression of TNF. By employing prostaglandin E{sub 2} and low concentrations of phorbol 12-myristate 13-acetate, a synergism in the induction of desensitization can be demonstrated. Hence, these studies show that two distinct pathways are involved in the induction of hyporesponsiveness. These data indicate that LPS-desensitized Mono-Mac-6 cells are able to activate initial steps of signal transduction up to the level of the NF-{kappa}B transcription factor. The absence of TNF transcripts, however, indicates that additional nuclear factors may be missing or that silencers may be active such that transcription of the TNF gene is prevented.

• OSTI ID: 5029604
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:24; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
ACTINOMYCIN
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CARCINOGENS
CELL KILLING
CHROMIUM 51
CHROMIUM ISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENZYMES
ESTERS
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LIPIDS
LIPOPOLYSACCHARIDES
MATERIALS
MOLECULAR BIOLOGY
MONOCYTES
NECROSIS
NEOPLASMS
NUCLEI
NUCLEOPROTEINS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PHORBOL ESTERS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYSACCHARIDES
PROSTAGLANDINS
PROTEINS
RADIOASSAY
RADIOISOTOPES
SACCHARIDES
SYNERGISM
TRANSCRIPTION FACTORS
TRANSFERASES