CC
趨化激素 Eotaxin-1 與骨關節炎病程相關性之探討 本論文主要在探討 CC 趨化激素中 Eotaxin-1 與骨關節炎致病過程之相關性。
初步篩檢骨關節炎患者後，發現患者血漿中 CC 趨化激素 RANTES 、 MCP-1 a 、 Eotaxin-1 濃度均較正常人高。在三次高分子玻尿酸注射治療過程中，患 者血漿中 RANTES 及 MCP-1a 濃度均有隨著治療而降低的趨勢，而 Eotaxin-1 雖然在第一次治療後濃度明顯降低，但是其血漿濃度卻有慢慢回復的趨勢。
利用 RT-PCR 及 ELISA ，我們發現 IL-1b 及 TNF-a 刺激軟骨細胞會誘使細胞 表現 Eotaxin-1 mRNA ，且可持續分泌 Eotaxin-1 ；進一步用 Eotaxin-1 刺激軟 骨細胞後，發現軟骨細胞間質分解酵素 MMP-3 、 MMP-13 的 mRNA 表現隨 著 Eotaxin-1 濃度增加而增加，但間質分解酵素抑制蛋白（ TIMP-1 ）的 mRN A 表現卻沒有明顯變化。除此之外，我們還用 RT-PCR 及流式細胞儀分析 Eot axin-1 對軟骨細胞上趨化激素接受體 CCR3 、 CCR5 表現的影響，發現隨著 E otaxin-1 濃度增加會明顯促進 CCR3 mRNA 及細胞膜上 CCR3 的表現，不過 E otaxin-1 雖然可些微促進細胞膜上 CCR5 的表現，但對 CCR5 mRNA 的表現沒 有影響。綜合以上結果，我們首次發現人類軟骨細胞能表現 Eotaxin-1 ，且 E otaxin-1 可能經由促進間質分解酵素 MMP-3 、 MMP-13 及趨化激素接受體 C CR3 表現而參與調控軟骨細胞的間質分解功能，進一步造成關節組織受損，
與骨關節炎致病過程有一定的關聯。
Studies on the Relationship between the CC Chemokine Eotaxin-1 and the Progression of Osteoarthritis
We studied on the relationship between CC chemokine Eotaxin-1 and the progressi on of osteoarthritis. The concentrations of RANTES, MCP-1a and Eotaxin-1 in pati ents’ plasma with osteoarthritis (OA) are higher than those in normal plasma. Both the concentrations of RANTES and MCP-1a were decreased during injection of hy aluronan three times in patients with OA, while the concentration of Eotaxin-1 was significantly decreased at first time then it reversed. By reverse transcription-polym erase chain reaction (RT-PCR) and enzyme-linked immunosorbat assay (ELISA), we found that the expression of Eotaxin-1 mRNA in chondrocytes was induced by i nterlukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a). Besides Eotaxin-1 was c onstitutively secreted after stimulation with IL-1b and TNF-a. Furthermore, Eotaxi n-1 increased matrix metalloproteinase-3 (MMP-3) and MMP-13 messenger RNA (mRNA) expression but had no effect on TIMP-1 mRNA expression in chondrocyt es. Eotaxin-1 induced both the expressions of CCR3 and CCR5 on cell surface, whi ch analyzed by flow cytometry. Chondrocytes expressed CCR3 mRNA after stimul ation with Eotaxin-1 while CCR5 mRNA was undetectable. To our knowledge, this is the first time to find human chondrocytes produce Eotaxin-1 in our study. We su ggested that Eotaxin-1 might involve in cartilage degradation by inducing the expre ssion of matrix metalloproteinases and CCR3.
