Research article
Candida albicans induces cyclo-oxygenase 2 expression and prostaglandin E2 production in synovial fibroblasts through an extracellular-regulated kinase 1/2 dependent pathway
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* Corresponding author: Herng-Sheng Lee herngsheng131419@gmail.com
1 Department of Pathology, Tri-Service General Hospital and National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd, Neihu District, Taipei City 114, Taiwan
2 Graduate Institute of Pathology and Parasitology, National Defense Medical Center, No. 161, Minchun E. Rd, Neihu District, Taipei City 114, Taiwan
3 School of Public Health, National Defense Medical Center, No. 161, Minchun E. Rd, Neihu District, Taipei City 114, Taiwan
4 Osteoarticular Research Group, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
Arthritis Research & Therapy 2009, 11:R48 doi:10.1186/ar2661
Published: 29 March 2009Abstract
Introduction
Synovial 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.
Methods
Primary 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.
Results
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 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.
Conclusions
C. 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.