Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-α

Carolyn H. Srivastava, Thomas A. Rado, Deborah Bauerle, Hal Broxmeyer

Research output: Contribution to journalArticle

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Abstract

Lactoferrin (LF) and myeloperoxidase (MPO) are glycoproteins synthesized in early myeloid cells (promyelocytes, myelocytes) and stored in granules of polymorphonuclear neutrophilic granulocytes. Both proteins are involved in the host inflammatory response, and LF has been found to have myelosuppressive activity in vivo and in vitro. Little is known, however, about the regulation of their production. We investigated the stability of LF and MPO mRNA and the effects of purified recombinant human TNF-α on LF and MPO levels in normal human bone marrow. Low density human bone marrow cells were cultured in the presence or absence of actinomycin D(10 μg/ml) or TNF-α (200 U/ml). LF and MPO RNA levels were analyzed by Northern blots using, respectively, a 650-bp insert from the plasmid pHL41, and a 2.3-kb insert from the plasmid pMPO2 as probes. It was found that: 1) LF mRNA is a fairly stable molecule, with a half-life of between 8 and 9 h, whereas MPO is less stable, with a half-life of between 4 and 5 h; 2) TNF-α decreases both LF and MPO mRNA levels, an effect seen by 24 h with MPO mRNA and 48 h with LF mRNA; 3) nuclear run-on assays revealed that TNF decreases transcription of the LF gene by 70% and the MPO gene by 50%; and 4) the suppressive effect of TNF-α on LF and MPO mRNA levels is not due to cell killing or selective differentiation and is reversible.

Original languageEnglish
Pages (from-to)1014-1019
Number of pages6
JournalJournal of Immunology
Volume146
Issue number3
StatePublished - Feb 1 1991

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Lactoferrin
Peroxidase
Tumor Necrosis Factor-alpha
Bone Marrow
Gene Expression
Messenger RNA
Granulocyte Precursor Cells
Half-Life
Plasmids
Dactinomycin
Myeloid Cells
Granulocytes
Bone Marrow Cells
Northern Blotting
Genes
Glycoproteins
RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-α. / Srivastava, Carolyn H.; Rado, Thomas A.; Bauerle, Deborah; Broxmeyer, Hal.

In: Journal of Immunology, Vol. 146, No. 3, 01.02.1991, p. 1014-1019.

Research output: Contribution to journalArticle

Srivastava, Carolyn H. ; Rado, Thomas A. ; Bauerle, Deborah ; Broxmeyer, Hal. / Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-α. In: Journal of Immunology. 1991 ; Vol. 146, No. 3. pp. 1014-1019.
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