Pro-inflammatory cytokines stimulate stromal derived factor-1 (sdf-1?) expression in cultured synoviocytes from human subacromial bursa

Purpose Chemokines produced by synoviocytes of the subacromial bursa are up-regulated in subacromial inflammation (bursitis) and rotator cuff disease. SDF-1a is an important chemotactic factor in the subacromial bursa that stimulates recruitment of inflammatory cells; however, its mechanism of induction and regulation in the subacromial bursa is unknown. We hypothesised that SDF-1a production in bursal synoviocytes may be induced by local cytokines such as interleukin IL-1β and IL-6. Methods Subacromial bursa specimens were obtained following an institutional review board-approved protocol from patients undergoing shoulder surgery. Bursal specimens were stained with anti-human antibodies to IL-1, IL-6 and SDF-1a by immunohistochemistry and compared to normal and rheumatoid controls. Bursal cells were also isolated from specimens and cultured. Cultured cells were labelled with fluorescent probes and analysed by flow cytometry to determine cell lineage. Early-passaged cells were then treated with cytokines IL-1β and IL-6 and SDF-1a production and expression were measured by ELISA and RT-PCR. Results SDF-1a, IL-1β and IL-6 were expressed at high levels in bursitis specimens from human subacromial bursa compared to normal controls. In bursal synoviocytes, there was a dose-dependent increase in SDF-1a production in the supernatants of cells treated with IL-1β. SDF-1a mRNA expression was also increased in bursal cells treated with IL-1β, with stimulation occurring at 6 hours and increasing to five-fold stimulation by 48 hours. IL-6 caused a minimal but not statistically significant increase in SDF-1a expression. Conclusion SDF-1a, IL-1β, and IL-6 are expressed in the inflamed human subacromial bursal tissues in patients with subacromial bursitis. In cultured bursal synoviocytes, SDF-1a production is stimulated by IL-1β. These cytokines may stimulate or potentiate the inflammatory response that occurs in subacromial bursitis and rotator cuff disease, and may provide a potential new target mechanism for inhibition of this common clinical problem.