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Nature. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production.

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  • Nature. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production.

    Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production - Nature Medicine
    Nature Medicine 15, 42 - 49 (2008)
    Published online: 21 November 2008 | doi:10.1038/nm.1905

    Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production

    Krisztián Németh 1,6, Asada Leelahavanichkul 2,6, Peter S T Yuen 2, Balázs Mayer 1, Alissa Parmelee 1, Kent Doi 2, Pamela G Robey 1, Kantima Leelahavanichkul 1, Beverly H Koller 4, Jared M Brown 5, Xuzhen Hu 2, Ivett Jelinek 3, Robert A Star 2,6 & Éva Mezey 1,6

    Abstract

    Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function.
    The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor.
    Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice.
    Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2.
    Our results suggest that BMSCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors.
    Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.

    1. National Institute of Dental and Craniofacial Research (NIDCR), Craniofacial and Skeletal Diseases Branch, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA
    2. National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Renal Diagnostics and Therapeutics Unit, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA
    3. National Cancer Institute (NCI), Experimental Immunology Branch, US National Institutes of Health (NIH), 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.
    4. Department of Genetics, University of North Carolina, 4341 Medical Biomolecular Research Building, Chapel Hill, North Carolina 27599, USA.
    5. Department of Pharmacology and Toxicology, East Carolina University, Greenville, North Carolina 27858, USA.
    6. These authors contributed equally to this work.

    Correspondence to: Éva Mezey1,6 e-mail: mezeye@mail.nih.gov
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    <cite cite="http://www.nature.com/nm/journal/v15/n1/abs/nm.1905.html">Bone marrow stromal cells attenuate sepsis via prostaglandin E: 2: -dependent reprogramming of host macrophages to increase their interleukin-10 production : Abstract : Nature Medicine</cite>
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