Production and distribution of interleukin 15 and its receptors (IL-15Ralpha and IL-R2beta) in the implant interface tissues obtained during revision of failed total joint replacement.
Failure of total joint replacement (TJR) is a major problem and it is estimated that 15-20% of TJR will fail within 5-10 years after implantation. Most TJR is attributed to aseptic loosening of the implants in association with resorption of related bone due to the release of bone-associated cytokines. IL-15 is a cytokine that activates T cells and natural killer (NK) cells. IL-15 protein is ubiquitous and is expressed in many tissues and cell types. Using immunohistochemical techniques, we demonstrated the expression of IL-15 and its receptors IL-15Ralpha and IL-2Rbeta in the interface tissues obtained from revision surgery. Both IL-15 protein and IL-15Ralpha were observed in macrophages, multinucleated giant cells and endothelial cells around blood vessels. Both the SDS-PAGE and western blot revealed multiple bands and after stages of glycosylation, this resulted in a band at 13 KDa which corresponds to the IL-15 protein. Again RT-PCR results demonstrated a band of 420 bp corresponding to the IL-15 protein. In addition, using U937 cells, the expression of both IL-15 protein and IL-15Ralpha were considerably up-regulated when challenged with retrieved metal particles. Our results illustrated the IL-15 to be an intact protein and that it is stored in the cytoplasm. A dye exclusion cell viability test displayed an increase in toxicity with an increase in the amount of metal particles added. There was a discrepancy between abundant IL-15 mRNA, intracellularly detectable IL-15 protein and apparently inefficient secretion. This suggests that IL-15 protein production is predominantly regulated post-transcriptionally and this is indicated by its strict regulation, especially at cell trafficking. Finally, unlike IL-2, IL-15 plays a certain role in bone resorption that leads to failed joint prostheses. It is apparent that this cytokine is an important T cell mediated immune response which needs further research.
Saeed
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Osteoarticular Research Group and IRC in Biomedical Materials, Department of Histopathology, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
Revell
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PA
D000368:Aged; D001168:Arthritis / Q000276:immunology*; D019643:Arthroplasty, Replacement; D015153:Blotting, Western; D001862:Bone Resorption; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008670:Metals; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000032:analysis; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
C508024:IL15RA protein, human; D019409:Interleukin-15; D008670:Metals; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2