PMID- 15459235 OWN - NLM STAT- MEDLINE DCOM- 20050125 LR - 20171116 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 76 IP - 6 DP - 2004 Dec TI - Recombinant HLA-G5 and -G6 drive U937 myelomonocytic cell production of TGF-beta1. PG - 1220-8 AB - 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-gamma (IFN-gamma), 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-gamma-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-beta1. 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 alpha, IL-1beta, 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. FAU - McIntire, Ramsey H AU - McIntire RH AD - Departments of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. FAU - Morales, Pedro J AU - Morales PJ FAU - Petroff, Margaret G AU - Petroff MG FAU - Colonna, Marco AU - Colonna M FAU - Hunt, Joan S AU - Hunt JS LA - eng GR - HD26429/HD/NICHD NIH HHS/United States GR - HD33994/HD/NICHD NIH HHS/United States GR - HD35859/HD/NICHD NIH HHS/United States GR - HD39878/HD/NICHD NIH HHS/United States GR - P20 RR16475/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040930 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Antigens, CD) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (LILRB1 protein, human) RN - 0 (LILRB2 protein, human) RN - 0 (Leukocyte Immunoglobulin-like Receptor B1) RN - 0 (Membrane Glycoproteins) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Immunologic) RN - 0 (Recombinant Fusion Proteins) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Antigens, CD/immunology/metabolism MH - Cell Differentiation/drug effects/immunology MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects/immunology MH - Female MH - HLA Antigens/genetics/*immunology/pharmacology MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/genetics/*immunology/pharmacology MH - Humans MH - Immune Tolerance/immunology MH - Interferon-gamma/pharmacology MH - Interleukin-10/biosynthesis MH - Leukocyte Immunoglobulin-like Receptor B1 MH - Macrophages/drug effects/*immunology/metabolism MH - Membrane Glycoproteins MH - Monocytes/drug effects/*immunology/metabolism MH - Pregnancy MH - Protein Binding/drug effects/immunology MH - Protein Isoforms/genetics/metabolism/pharmacology MH - Receptors, Immunologic/immunology/metabolism MH - Recombinant Fusion Proteins/genetics/immunology/pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transforming Growth Factor beta/*biosynthesis MH - Transforming Growth Factor beta1 MH - U937 Cells EDAT- 2004/10/02 05:00 MHDA- 2005/01/26 09:00 CRDT- 2004/10/02 05:00 PHST- 2004/10/02 05:00 [pubmed] PHST- 2005/01/26 09:00 [medline] PHST- 2004/10/02 05:00 [entrez] AID - jlb.0604337 [pii] AID - 10.1189/jlb.0604337 [doi] PST - ppublish SO - J Leukoc Biol. 2004 Dec;76(6):1220-8. doi: 10.1189/jlb.0604337. Epub 2004 Sep 30.