Vitamin D-binding protein deficiency in mice decreases systemic and select tissue levels of inflammatory cytokines in a murine model of acute muscle injury.
J Trauma Acute Care Surg
; 84(6): 847-854, 2018 06.
Article
en En
| MEDLINE
| ID: mdl-29554047
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína de Unión a Vitamina D
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Citocinas
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Músculo Esquelético
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Trauma Acute Care Surg
Año:
2018
Tipo del documento:
Article