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Recombinant HLA‐G5 and ‐G6 drive U937 myelomonocytic cell production of TGF‐β1
Author(s) -
McIntire Ramsey H.,
Morales Pedro J.,
Petroff Margaret G.,
Colonna Marco,
Hunt Joan S.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0604337
Subject(s) - biology , recombinant dna , u937 cell , transforming growth factor , immunology , cancer research , microbiology and biotechnology , cell culture , genetics , gene
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.