PILOT 2 CHEMOKINE EXPRESSION REGULATION IN HUMAN SUBACROMIAL BURSA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chemokine expression and regulation in human subacromial bursa Abstract: Recent investigations have identified the presence of chemokines (tumor necrosis factor alpha, interleukin 1, interleukin 6, cyclooxygenases (COX-2) in synoviocytes of the subacromial bursa, several of which are up-regulated in bursitis tissue compared to normal controls. These studies have identified a novel role for SDF-1, a potent chemotactic and angiogenic factor that stimulates recruitment of inflammatory cells. The expression of SDF-1 in the bursal synoviocyte in culture may be induced and regulated by mechanical, environmental and chemical stimuli. Currently, the mechanisms by which these stimuli lead to subacromial inflammation and SDF-1 expression in the bursal synoviocyte are unknown. The goal of the present study will be to determine the mechanisms of SDF-1 induction by external stimuli. Cell signaling processes important for SDF-1 expression will be assessed using signal transduction inhibitors. The pathways of inhibition will be further examined using prostaglandins, cox-2 inhibitors, and corticosteroids. Finally, in an effort to develop targeted inhibition of subacromial bursitis, the potential role for SDF-1 inhibitors including small interfering RNA (siRNA) on SDF-1 expression in the bursal synoviocyte will be examined. Due to the high prevalence of shoulder pain (over 6 million office visits per year) and the common use of non-selective pharmacologic agents which carry significant risk of side effects (NSAIDs and steroids), this project has important clinical relevance in the treatment of shoulder impingement syndrome, one of the most common musculoskeletal diseases.