Abstract
IntroductionSynovial cells are potential sources of inflammatory mediators in bacterial-induced arthritis but their involvement in the inflammatory response to Candida albicans-induced septic arthritis is largely unknown.MethodsPrimary cultures of rat synovial fibroblasts were infected with C. albicans (ATCC90028). Immunocytochemistry, western blotting, and RT-PCR were performed to assess cyclo-oxygenase 2 induction. Phosphorylation of extracellular-regulated kinase (ERK1/2) following infection in the absence or presence of U0126 was assessed by western blotting whilst prostaglandin E2 production was measured by ELISA. Nuclear factor κB (NFκB) translocation was evaluated by an electrophoretic mobility shift assay.ResultsInfection of synovial fibroblasts with C. albicans resulted in cyclo-oxygenase 2 expression and prostaglandin E2 production. Cyclo-oxygenase 2 expression and prostaglandin E2 production was dependent upon extracellular-regulated kinase 1/2 phosphorylation, associated with activation of NFκB and significantly elevated in the presence of laminarin, an inhibitor of dectin-1 activity. Synovial fibroblasts adjacent to C. albicans hyphae aggregates appeared to be the major contributors to the increased levels of cyclo-oxygenase 2 and phosphorylated extracellular-regulated kinase 1/2.ConclusionsC. albicans infection of synovial fibroblasts in vitro results in upregulation of cyclo-oxygenase 2 and prostaglandin E2 by mechanisms that may involve activation of extracellular-regulated kinase 1/2 and are associated with NFκB activation.
Highlights
Synovial cells are potential sources of inflammatory mediators in bacterial-induced arthritis but their involvement in the inflammatory response to Candida albicansinduced septic arthritis is largely unknown
Infection of synovial fibroblasts with C. albicans resulted in cyclo-oxygenase 2 expression and prostaglandin E2 production
Cyclo-oxygenase 2 expression and prostaglandin E2 production was dependent upon extracellular-regulated kinase 1/2 phosphorylation, associated with activation of Nuclear factor κB (NFκB) and significantly elevated in the presence of laminarin, an inhibitor of dectin-1 activity
Summary
Synovial cells are potential sources of inflammatory mediators in bacterial-induced arthritis but their involvement in the inflammatory response to Candida albicansinduced septic arthritis is largely unknown. Articular structures can be affected by mycotic infections through direct inoculation, contiguous spread, or hematogenous dissemination [1,2,3,4]. Experimental arthritis in Sprague-Dawley rats with intravenous administration of C. albicans demonstrates that Candida arthritis involves joint tissues and adjacent bones [9]. Direct inoculation of joints with C. albicans results in a rapidly progressive septic arthritis that exacerbates collagen-induced arthritis [10]. Fungal infection may induce and exacerbate autoimmune diseases such as rheumatoid arthritis potentially through effects of β-glucans, polysaccharides in the cell wall of fungi, on inflammatory and immune responses [11]
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