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Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis
- Source :
- American Journal of Pathology; January 2016, Vol. 186 Issue: 1 p57-66, 10p
- Publication Year :
- 2016
-
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-1β expression but promoted expression of CD163, transforming growth factor-β1, 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.
Details
- Language :
- English
- ISSN :
- 00029440
- Volume :
- 186
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- American Journal of Pathology
- Publication Type :
- Periodical
- Accession number :
- ejs37245037
- Full Text :
- https://doi.org/10.1016/j.ajpath.2015.09.006