ArticleCellular & molecular immunology2015
The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF-trophoblast-IL-10 axis via Stat1 inhibition and Stat3 activation.
Article in Cellular & molecular immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- Hydroxychloroquine Effects on THP-1 Macrophage Cholesterol Handling: Cell Culture Studies Corresponding to the TARGET Cardiovascular Trial.Medicina (Kaunas, Lithuania) · 2022Trial
- LIF and Oncostatin M mitigate LPS-induced acute endometritis via distinct immunoregulatory mechanisms in peritoneal macrophagesiScience · 2026Article
- Human XIRP1 is a new podosome protein targeting cytosolic bacteria as part of the IFN-γ defense program.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- In Vitro Effects of the Three Actives IL-12 (5 CH), IFN-γ (6 CH), and TNF-α (5 CH) from the Micro-Immunotherapy Medicine 2LEID-NCurrent issues in molecular biology · 2026Article
- Luminal hormone-responsive cells tune the regenerative remodeling of mammary glands in large mammals.Cell discovery · 2025Article
- In Vivo Response of γδ T Cells and Macrophages to Non-Bilayer Phospholipid Arrangements in a Lupus-like Mouse Model.International journal of molecular sciences · 2025Article
- High content imaging shows distinct macrophage and dendritic cell phenotypes for psoriasis and atopic dermatitis.Scientific reports · 2025Article
- Machine learning selection of basement membrane-associated genes and development of a predictive model for kidney fibrosis.Scientific reports · 2025Article
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
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- Macrophage Transcriptomic Alterations Driven by Alphavirus-Based Cancer Immunotherapy Vectors.Journal of immunology research · 2025Article
- Profiling migration of human monocytes in response to chemotactic and barotactic guidance cues.Cell reports methods · 2024Article
- Unveiling the immune dynamics ofInfection and immunity · 2024Article
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- Tumor ABCC4-mediated release of PGE2 induces CD8International journal of biological sciences · 2024Article
- Anemoside A3 Inhibits Macrophage M2-Like Polarization to Prevent Triple-Negative Breast Cancer Metastasis.Molecules (Basel, Switzerland) · 2023Article
- Robust single-cell matching and multimodal analysis using shared and distinct features.Nature methods · 2023Article
- Research progress on the STAT signaling pathway in pregnancy and pregnancy-associated disorders.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon gamma (IFN-γ) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-γ induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-γ on macrophage activation. IFN-γ reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT+LIF cells) and BeWo cells (BW/ST+LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-γ. vCT+LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST+LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-γ on monocyte/macrophage motility. BW/ST+LIF cells also generate IFN-γ-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-α), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-γ-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF-trophoblast-IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.
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