Macrophage polarization in IL-10 treatment of particle-induced inflammation and osteolysis

dc.contributor.authorJiang, Jianhao
dc.contributor.authorJia, Tanghong
dc.contributor.authorGong, Weiming
dc.contributor.authorNing, Bin
dc.contributor.authorWooley, Paul H.
dc.contributor.authorYang, Shang-You
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractThis 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-1 beta expression but promoted expression of CD163, transforming growth factor-beta 1, and CCR2. Furthermore, IL-10 significantly inhibited the ultra-high-molecular-weight polyethylene particle-elevated phospho-STAT1 and phospho NF-kappa B 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 NE-kappa B and Janus activating kinase/STAT1 expression.en_US
dc.description.sponsorshipOrthopedic Research Institute Via Christi St. Francis Hospital, and a grant from the Orthopaedic Research and Education Foundation (S.-Y.Y.).en_US
dc.identifier.citationJianhao Jiang, Tanghong Jia, Weiming Gong, Bin Ning, Paul H. Wooley, Shang-You Yang, Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis, The American Journal of Pathology, Volume 186, Issue 1, January 2016, Pages 57-66en_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofseriesAmerican Journal of Pathology;v.186:no.1
dc.rights.holderCopyright © 2016 Elsevier B.V. or its licensors or contributors.en_US
dc.subjectDebris-induced osteolysisen_US
dc.subjectVIL-10 gene-transferen_US
dc.subjectMurine air pouchen_US
dc.subjectAlternative activationen_US
dc.subjectTitanium particlesen_US
dc.subjectWear particlesen_US
dc.titleMacrophage polarization in IL-10 treatment of particle-induced inflammation and osteolysisen_US
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