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Suppression of Skeletal Muscle Inflammation by Muscle Stem Cells
Author(s) -
Proto Jonathan,
Lu Aiping,
Imbrogno Kayla,
Tang Ying,
Robbins Paul,
Wang Bing,
Huard Johnny
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1034.8
Subject(s) - inflammation , tumor necrosis factor alpha , stem cell , skeletal muscle , microbiology and biotechnology , cytokine , in vivo , chemistry , in vitro , hepatocyte growth factor , cell growth , cancer research , biology , immunology , endocrinology , biochemistry , receptor
Recently, we have reported that intramuscular (i.m.) injection of muscle‐derived stem cells (MDSCs) heterozygous for the NF‐kB subunit p65 (p65 +/− ) reduces host inflammation and fiber necrosis following muscle injury more so than wild type (WT) MDSC injection. In vitro inflammation assays demonstrated that MDSCs secrete factors that modulate cytokine expression in LPS‐activated macrophages, and genetic reduction of p65 enhances this effect. We have also found that the anti‐inflammatory protein hepatocyte growth factor is more highly expressed in p65 +/− cells. In order to investigate the impact of these observations in vivo , we performed i.m. injections of WT or p65 +/− MDSCs into WT mouse muscle 24 hrs post injury. We followed cell fate at 1, 3, and 7 days post‐injection. At 24 hrs we observed a higher number of engrafting WT cells, but a higher percentage of proliferating (Ki67+) p65 +/− MDSCs. By 3, and 7 days, the number of p65 +/− MDSCs exceeded that of WT cells. These preliminary results suggest a novel role for NF‐kB in stem cells, one in which the anti‐inflammatory properties of MDSCs are regulated by NF‐kB via growth factor expression and cell proliferation kinetics. Grant Funding Source : Department of Defense