CC趨化激素Eotaxin-1與骨關節炎病程相關性之探討

Studies on the Relationship between the CC Chemokine Eotaxin-1 and the Progression of Osteoarthritis

李昭儀(Li, Chao Yi)

指導教授 ： 陳建和

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2002年)

摘要

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-1a、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mRNA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Eotaxin-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Eotaxin-1濃度增加會明顯促進CCR3 mRNA及細胞膜上CCR3的表現，不過Eotaxin-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Eotaxin-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CCR3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。

關鍵字

趨化激素 ； 骨關節炎 ； 退化性關節炎 ； 間質分解酵素 ； 趨化激素接受體

並列摘要

We studied on the relationship between CC chemokine Eotaxin-1 and the progression of osteoarthritis. The concentrations of RANTES, MCP-1a and Eotaxin-1 in patients’ plasma with osteoarthritis (OA) are higher than those in normal plasma. Both the concentrations of RANTES and MCP-1a were decreased during injection of hyaluronan three times in patients with OA, while the concentration of Eotaxin-1 was significantly decreased at first time then it reversed. By reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbat assay (ELISA), we found that the expression of Eotaxin-1 mRNA in chondrocytes was induced by interlukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a). Besides Eotaxin-1 was constitutively secreted after stimulation with IL-1b and TNF-a. Furthermore, Eotaxin-1 increased matrix metalloproteinase-3 (MMP-3) and MMP-13 messenger RNA (mRNA) expression but had no effect on TIMP-1 mRNA expression in chondrocytes. Eotaxin-1 induced both the expressions of CCR3 and CCR5 on cell surface, which analyzed by flow cytometry. Chondrocytes expressed CCR3 mRNA after stimulation 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 suggested that Eotaxin-1 might involve in cartilage degradation by inducing the expression of matrix metalloproteinases and CCR3.

並列關鍵字

chemokine ； osteoarthritis ； Eotaxin-1 ； matrix metalloproteinase ； CCR3

參考文獻

Aigner, T., and McKenna, L. (2002) Molecular pathology and pathobiology of osteoarthritis cartilage. Cell. Mol. Life. Sci. 59:5-18.

Andrew, D.L. (2002) The role of chemokines in linking innate and adaptive immunity. Curr. Opin. Immunol. 14:129-35.

Review. Arend, W.P., and Dayer, J-M. (1995) Inhibition of the production and effects of interleukin-1 and tumor necrosis factora in rheumatoid arthritis. Arthritis. Rheum. 38:151-60.

Review. Bacon, K.B., Szabo, M.C., Yssel, H., Bolen, J.B., and Schall, T.J. (1996) RANTES induces tyrosine kinase activity of stably complexed p125FEK and ZAP-70 in human T-cells. J. Exp. Med. 184:873-82.

Baggiolini, M. (1998) Chemokine and leukocyte traffic. Nature 392:565-8.