Paracrine in vivo inhibitory effects of adipose tissue–derived mesenchymal stromal cells in the early stages of the acute inflammatory response

Autor: Maria Isabel Guillén, María Carmen Carceller, María Luisa Ferrándiz, María José Alcaraz
Rok vydání: 2015
Předmět:
Male
Cancer Research
Chemokine
Leukocyte migration
Leukotriene B4
medicine.medical_treatment
Interleukin-1beta
Immunology
Fluorescent Antibody Technique
Adipose tissue
Enzyme-Linked Immunosorbent Assay
Inflammation
Mesenchymal Stem Cell Transplantation
Dinoprostone
Mice
Paracrine signalling
chemistry.chemical_compound
Cell Movement
Paracrine Communication
Leukocytes
medicine
Animals
Immunology and Allergy
Genetics (clinical)
Prostaglandin-E Synthases
Transplantation
biology
Interleukin-6
Tumor Necrosis Factor-alpha
Transcription Factor RelA
Zymosan
Mesenchymal Stem Cells
Cell Biology
Intramolecular Oxidoreductases
Adipose Tissue
Oncology
chemistry
Cyclooxygenase 2
Culture Media
Conditioned
Cancer research
biology.protein
Cytokines
Tumor necrosis factor alpha
medicine.symptom
Prostaglandin E
Zdroj: Cytotherapy. 17:1230-1239
ISSN: 1465-3249
Popis: Background aims Excessive or unresolved inflammation leads to tissue lesions. Adipose tissue–derived mesenchymal stromal cells (AMSCs) have shown protective effects that may be dependent on the modulation of inflammation by secreted factors. Methods We used the zymosan-induced mouse air pouch model at two time points (4 h and 18 h) to evaluate the in vivo effects of AMSCs and their conditioned medium (CM) on key steps of the early inflammatory response. We assessed the effects of AMSCs and CM on leukocyte migration and myeloperoxidase activity. The levels of chemokines, cytokines and eicosanoids in exudates were measured by use of enzyme-linked immunoassay or radio-immunoassay. In addition, the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1) was studied by use of Western blotting and the phosphorylation of p65 nuclear factor-κB (NF-κB) by immunofluorescence. Results All inflammatory parameters were significantly reduced by CM and AMSCs to a similar extent at 4 h after zymosan injection with lower effects at 18 h. The observed inhibition of leukocyte migration was associated with reduced levels of chemokines and leukotriene B 4 . Interleukin-1β, interleukin-6, tumor necrosis factor-α and tumor necrosis factor–stimulated gene 6 levels were significantly decreased. The downregulation of mPGES-1 was associated with inhibition of prostaglandin E 2 production. Our results suggest that these anti-inflammatory effects are related, in part, to the inhibition of NF-κB activation. Conclusions AMSCs dampen the early process of inflammation in the zymosan-induced mouse air pouch model through paracrine mechanisms. These results support the potential utility of these cells as a source of novel treatment approaches for inflammatory pathologies.
Databáze: OpenAIRE
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