title: Macrophage Polarization in IL-10 Treatment of Particle-Induced Inflammation and Osteolysis.
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.
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, Kansas; Department of Orthopaedics, Jinan Central Hospital, Shandong University, Jinan, China.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics, Jinan Central Hospital, Shandong University, Jinan, China.
authors.forename: Tanghong
authors.initials: T
authors.lastname: Jia
authors.affiliation: Department of Orthopaedics, Jinan Central Hospital, Shandong University, Jinan, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Orthopaedics, Jinan Central Hospital, Shandong University, Jinan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ning
authors.affiliation: Department of Orthopaedic Surgery, University of Kansas School of Medicine, Wichita, Kansas.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wooley
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, Kansas; Department of Orthopaedic Surgery, University of Kansas School of Medicine, Wichita, Kansas. Electronic address: shang-you.yang@wichita.edu.
authors.forename: Shang-You
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000818:Animals; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010014:Osteolysis / Q000276:immunology* / Q000473:pathology; D011095:Polyethylenes / Q000009:adverse effects; D011183:Postoperative Complications / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D055114:X-Ray Microtomography
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D016753:Interleukin-10