PILOT 2 CHEMOKINE EXPRESSION REGULATION IN HUMAN SUBACROMIAL BURSA

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 趋化因子在人肩峰下囊中的表达与调控 摘要： 最近的研究已经确定了肩峰下囊的滑膜细胞中存在趋化因子（肿瘤坏死因子α、白细胞介素1、白细胞介素6、环加氧酶（考克斯-2）），与正常对照相比，其中几种在滑囊炎组织中上调。 这些研究已经确定了SDF-1的新作用，SDF-1是一种有效的趋化和血管生成因子，可刺激炎症细胞的募集。在体外培养的腔上囊滑膜细胞中，SDF-1的表达可能受到机械刺激、环境刺激和化学刺激的诱导和调节。 目前，这些刺激导致肩峰下炎症和囊滑膜细胞中SDF-1表达的机制尚不清楚。 本研究的目的是确定SDF-1的诱导机制，由外部刺激。 将使用信号转导抑制剂评估对SDF-1表达重要的细胞信号传导过程。 抑制途径将进一步检查使用三尖杉酯碱，考克斯-2抑制剂，和皮质类固醇。 最后，在开发肩峰下滑囊炎的靶向抑制的努力中，将检查SDF-1抑制剂包括小干扰RNA（siRNA）对滑囊囊滑膜细胞中SDF-1表达的潜在作用。 由于肩痛的高患病率（每年超过600万次门诊就诊）和非选择性药物（NSAID和类固醇）的普遍使用，这些药物具有显著的副作用风险，因此该项目在治疗肩撞击综合征（最常见的肌肉骨骼疾病之一）方面具有重要的临床意义。

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.