Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production
| Autor: | Eva Mezey, Kent Doi, Krisztián Németh, Peter S.T. Yuen, Xuzhen Hu, Robert A. Star, Jared M. Brown, Pamela Gehron Robey, Balázs Mayer, Ivett Jelinek, Kantima Leelahavanichkul, Alissa Parmelee, Beverly H. Koller, Asada Leelahavanichkul |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Stromal cell medicine.medical_treatment Prostaglandin E2 receptor Prostaglandin Bone Marrow Cells Wounds Penetrating Models Biological Article General Biochemistry Genetics and Molecular Biology Dinoprostone chemistry.chemical_compound Mice stomatognathic system Sepsis medicine Animals Cecal Diseases Humans Cecum Bone Marrow Transplantation Mice Inbred BALB C Transplantation business.industry Macrophages Mesenchymal stem cell hemic and immune systems General Medicine Cellular Reprogramming Survival Analysis Interleukin-10 Mice Inbred C57BL Interleukin 10 medicine.anatomical_structure chemistry Immunology Tumor necrosis factor alpha Bone marrow Stromal Cells business Prostaglandin E |
| DOI: | 10.17615/gzd6-hp93 |
| Popis: | 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 E(2) 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. |
| Databáze: | OpenAIRE |
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