Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis.
Am J Pathol
; 186(1): 57-66, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26597885
ABSTRACT
This study investigated the therapeutic influence and potential mechanism of IL-10 in ameliorating orthopedic debris particle-induced inflammation and osteolysis. A murine air pouch with bone implantation and polyethylene particles was also used to evaluate the therapeutic effects of IL-10. The data suggested that the particle challenges significantly promoted macrophage activation and osteoclastogenesis, with dramatically increased macrophage infiltration into the pouch membranes and elevated tartrate-resistant acid phosphatase-positive cell deposition. Immunohistochemical stains revealed a significantly higher ratio of induced nitric oxide synthase-expressing cells in the particle-challenged group; treatment with IL-10 resulted in marked switching to CD163(+) cells. Also, IL-10 effectively reduced tartrate-resistant acid phosphatase-positive stained cells in the pouch membranes, and minimized the bone mineral density loss compared with untreated samples. Real-time PCR and Western blot examination indicated that IL-10 treatment significantly diminished the particle-induced IL-1ß expression but promoted expression of CD163, transforming growth factor-ß1, and CCR2. Furthermore, IL-10 significantly inhibited the ultra-high-molecular-weight polyethylene particle-elevated phospho-STAT1 and phospho-NF-κB p65 productions, and promoted phospho-STAT3 expression. Overall, the data indicate the pivotal effects of IL-10 on macrophage polarization. The effects of IL-10 in ameliorating local inflammation and osteolysis may be associated with macrophage polarization through the up-regulation of the Janus activating kinase/STAT3 signaling pathway, and the down-regulation of NF-κB and Janus activating kinase/STAT1 expression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteólise
/
Complicações Pós-Operatórias
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Interleucina-10
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Artroplastia de Substituição
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Ativação de Macrófagos
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article