title: Intravenous transplantation of mesenchymal stromal cells has therapeutic effects in a sepsis mouse model through inhibition of septic natural killer cells.
abstract: Transplantation of mesenchymal stromal cells is a promising strategy for treating sepsis. Natural killer cells are important in the development of sepsis, and their functions can be inhibited by mesenchymal stromal cells, we asked whether mesenchymal stromal cells exert their therapeutic effects through inhibiting the functions of natural killer cells in a septic mouse model generated with cecal ligation puncture method. Using co-cultures of cells, small interfering RNA, enzyme-linked immnuosorbent assays, fluorescence assays, western blotting, and pathological examination, we investigated the levels of inflammatory cytokines, proliferation of natural killer cells, inflammatory infiltration of important organs in mice, and activity of the Janus kinase/signal transducer and activator of transcription signaling pathway and found that mesenchymal stromal cells inhibited the function and proliferation of septic natural killer cells, increased interleukin-10 levels and increased the expression of components, such as Janus kinase 1, Janus kinase 2, and signal transducer and activator of transcription 3 in the Janus kinase/signal transducer and activator of transcription pathway both in vitro and in vivo. We conclude that mesenchymal stromal cells have their therapeutic effect in the septic mouse model through inhibiting the function and proliferation of septic natural killer cells. This biological process may involve interleukin-10 and suppressor of cytokine signaling 3 as well as other pathway components in the Janus kinase/signal transducer and activator of transcription pathway. Transplantation of mesenchymal stromal cells is an effective strategy to treat sepsis.
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China.
authors: Wenhua
authors: W
authors: Liu
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Yang
authors: Y
authors: Gao
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Haibo
authors: H
authors: Li
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Hongliang
authors: H
authors: Wang
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Ming
authors: M
authors: Ye
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China.
authors: Guihua
authors: G
authors: Jiang
authors: The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China; Depatment of Urology, Harbin Medical University Cancer Hospital, Harbin, Province Heilongjiang, China.
authors: Yongsheng
authors: Y
authors: Chen
authors: Depatment of Intensive Care Unit (ICU), The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Yang
authors: Y
authors: Liu
authors: Depatment of Emergency, The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Junying
authors: J
authors: Kong
authors: The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China.
authors: Wei
authors: W
authors: Liu
authors: The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China.
authors: Meng
authors: M
authors: Sun
authors: The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Province Heilongjiang, China; Depatment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Province Heilongjiang, China.
authors: Meng
authors: M
authors: Hou
authors: Department of intensive Care Unit (ICU), Harbin Medical University Cancer Hospital, Harbin, Province Heilongjiang, China. Electronic address: drkaijiang@163.com.
authors: Kaijiang
authors: K
authors: Yu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050791:STAT Transcription Factors / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism
chemical_list: D050791:STAT Transcription Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D016753:Interleukin-10; D053612:Janus Kinases
keywords: Interleukin-10; Mesenchymal stromal cell; Natural killer cell; Sepsis; Suppressor of cytokine signaling 3