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

C. H. Srivastava, T. A. Rado, D. Bauerle, H. E. Broxmeyer

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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 (US)
Pages (from-to)1014-1019
Number of pages6
JournalJournal of Immunology
Issue number3
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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