Fibroblast expression of C—C chemokines in response to orthopaedic biomaterial particle challenge in vitro

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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. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.