Vitamin D-binding protein deficiency in mice decreases systemic and select tissue levels of inflammatory cytokines in a murine model of acute muscle injury

被引:0
作者
Kew, Richard R. [1 ]
Tabrizian, Tahmineh [1 ]
Vosswinkel, James A. [2 ]
Davis, James E. [1 ]
Jawa, Randeep S. [2 ]
机构
[1] SUNY Stony Brook, Sch Med, Dept Pathol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Surg, Sch Med, Stony Brook, NY 11794 USA
基金
美国国家卫生研究院;
关键词
Actin; cytokines; inflammation; muscle injury; vitamin D-binding protein; GC-GLOBULIN; NEUTROPHIL HOMEOSTASIS; ORGAN DYSFUNCTION; ACTIN; PLASMA; RHABDOMYOLYSIS; CHEMOKINES; INFECTION; RESPONSES; BLOOD;
D O I
10.1097/TA.0000000000001875
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
BACKGROUND Severe acute muscle injury results in massive cell damage, causing the release of actin into extracellular fluids where it complexes with the vitamin D-binding protein (DBP). We hypothesized that a systemic DBP deficiency would result in a less proinflammatory phenotype. METHODS C57BL/6 wild-type (WT) and DBP-deficient (DBP-/-) mice received intramuscular injections of either 50% glycerol or phosphate-buffered saline into thigh muscles. Muscle injury was assessed by histology. Cytokine levels were measured in plasma, muscle, kidney, and lung. RESULTS All animals survived the procedure, but glycerol injection in both strains of mice showed lysis of skeletal myocytes and inflammatory cell infiltrate. The muscle inflammatory cell infiltrate in DBP-deficient mice had remarkably few neutrophils as compared with WT mice. The neutrophil chemoattractant CXCL1 was significantly reduced in muscle tissue from DBP-/- mice. However, there were no other significant differences in muscle cytokine levels. In contrast, plasma obtained 48 hours after glycerol injection revealed that DBP-deficient mice had significantly lower levels of systemic cytokines interleukin 6, CCL2, CXCL1, and granulocyte colony-stimulating factor. Lung tissue from DBP-/- mice showed significantly decreased amounts of CCL2 and CXCL1 as compared with glycerol-treated WT mice. Several chemokines in kidney homogenates following glycerol-induced injury were significantly reduced in DBP-/- mice: CCL2, CCL5, CXCL1, and CXCL2. CONCLUSIONS Acute muscle injury triggered a systemic proinflammatory response as noted by elevated plasma cytokine levels. However, mice with a systemic DBP deficiency demonstrated a change in their cytokine profile 48 hours after muscle injury to a less proinflammatory phenotype.
引用
收藏
页码:847 / 854
页数:8
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