title: Fibroblast expression of C-C chemokines in response to orthopaedic biomaterial particle challenge in vitro.
abstract: C-C chemokines are soluble mediators that occur in a periprosthetic granuloma and influence recruitment, localization and activation of inflammatory cells. This study tested effects of titanium and polymethylmethacrylate (PMMA) particles on expression of selected C-C chemokines in cultured human fibroblasts. The C-C chemokines analyzed included monocyte chemoattractant protein-1. 2 (MCP-1. 2), monocyte inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation, normal T-cell expressed and secreted protein (RANTES). Interleukin-1 beta (IL-1 beta) served as a known stimulator of chemokine release while interleukin-6 (IL-6) expression served as a marker for fibroblast activation. Protein and mRNA signal levels were determined by ELISA and RT-PCR, respectively. The results demonstrated that exposure of fibroblasts to titanium and PMMA particles resulted in increased release of MCP-1 in a dose- and time-dependent manner. After 24 h, titanium particles maximally upregulated MCP-1 release 7-fold while PMMA particles increased MCP-1 levels 2-fold, when compared to unchallenged fibroblasts. MCP-2, MIP-1 alpha and RANTES levels remained unchanged following exposure of fibroblasts to titanium or PMMA particles at any concentration or time point tested. However, IL-1 beta stimulated release of MCP-1, MCP-2, and RANTES, but not MIP-1 alpha from the fibroblasts. IL-1 beta, not particles, exhibited the most prominent effect on MCP-1 mRNA levels. Increased release of MCP-1 from fibroblasts exposed to titanium and PMMA particles coincided with increased release of IL-6. This study suggests that release of chemoattractant factors from fibroblasts localized in periprosthetic membranes enhances the chronic inflammatory process leading to bone resorption and implant loosening.
authors.affiliation: Orthopaedic Research Laboratory, Stanford University, School of Medicine, CA 94305-5341, USA.
authors.forename: B
authors.initials: B
authors.lastname: Yaszay
authors.forename: M C
authors.initials: MC
authors.lastname: Trindade
authors.forename: M
authors.initials: M
authors.lastname: Lind
authors.forename: S B
authors.initials: SB
authors.lastname: Goodman
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D001843:Bone Cements / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054412:Chemokine CCL8; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008422:Materials Testing; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism; D019904:Polymethyl Methacrylate / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014025:Titanium / Q000276:immunology* / Q000494:pharmacology*
chemical_list: D001843:Bone Cements; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054412:Chemokine CCL8; D019742:Chemokines, CC; D007375:Interleukin-1; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D019904:Polymethyl Methacrylate; D014025:Titanium