Recombinant HLA-G5 and -G6 drive U937 myelomonocytic cell production of TGF-β1

Ramsey H. McIntire, Pedro J. Morales, Margaret G. Petroff, Marco Colonna, Joan S. Hunt

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Throughout human pregnancy, activated maternal macrophages producing anti-inflammatory cytokines comprise a stable cell population in the uterus. This organ is also massively infiltrated with semiallogeneic, placenta-derived, invasive cytotrophoblast cells, which produce membrane and soluble isoforms of human leukocyte antigen (HLA)-G. Here, we investigated the possibility that two soluble isoforms of HLA-G, HLA-G5 and -G6, program macrophage production of cytokines. The model system consisted of human U937 myelomonocytic cells treated with phorbol 12-myristate 13-acetate (PMA) and interferon-γ (IFN-γ, which induced differentiation and activation but did not affect their viability or decrease their expression of the two inhibitory immunoglobulin-like transcript (ILT) receptors for HLA-G, ILT2 and ILT4. Exposure of the PMA/IFN-γ-treated U937 cells to increasing concentrations of recombinant HLA-G5 or -G6 (rG5 and rG6) stimulated effects common to the two isoforms. High doses of both significantly decreased interleukin (IL)-10 and dramatically increased transforming growth factor-β1. Differential effectiveness between the isoforms was demonstrated in dose-response studies, as was differential binding to ILT2 and ILT4 in receptor-blocking studies. No effects on production of IL-4, IL-1 receptor antagonist, IL-15, tumor necrosis factor α, IL-1β, or IL-6 were observed. Collectively, the results are consistent with the postulate that environmental programming of decidual macrophages may be dictated in part by their proximity to soluble HLA-G-producing fetal cytotrophoblast cells.

Original languageEnglish
Pages (from-to)1220-1228
Number of pages9
JournalJournal of Leukocyte Biology
Volume76
Issue number6
DOIs
StatePublished - Dec 1 2004

Keywords

  • Human
  • Macrophage cytokines
  • Pregnancy immunology

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