Studies on the expression of TLR2 and TLR4 on polymorphonuclear neutrophils and mononuclear cells and their soluble receptors, sTLR2 and sCD14, in the serum of patients with systemic lupus erythematosus

• Main Authors: Wei-Bo Liu, 劉韋博
• Other Authors: 余家利
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/61176052170213514404

碩士 === 臺灣大學 === 分子醫學研究所 === 95 === Toll-like receptors (TLRs), a recently discovered family of pattern recognition receptors, play an important role in mediating the activation of innate and adaptive immunity in vertebrate animals. TLRs express on a diverse variety of cells and tissues especially on dendritic cells, macrophages and granulocytes, recognizing pathogens like Gram-positive and -negative bacteria, viral RNA, unmethylated CpG DNA and fungi. Recent studies show that TLRs signaling is involved in either the initiation or the progression of systemic autoimmune disease and chronic inflammatory diseases. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease and its aetiology remains unclear. In this study, we investigate the expression of TLR2 and TLR4 on polymorphonuclear neutrophil (PMN) and mononuclear cell (MNC) in SLE patients and healthy subjects. We also try to identify the synergistic molecule related to TLR2 or TLR4 signaling and the mechanism involved in the pathogenesis of SLE. Our results show that the expression of TLR2 or TLR4 on PMN and MNC are not significantly different between healthy subjects and SLE patients. Nevertheless, we detect that the expression level of soluble CD14 (sCD14), the mediator of LPS-TLR4 signaling, in serum are significantly elevated in SLE patients. Moreover, we show that the expression level of soluble TLR2 (sTLR2), the modulator of TLR2 signaling, in serum are reduced in SLE patients. In addition, we utilize anti-TLR2 and anti-TLR4 antibodies to mimic immune stimulations to examine the immune response on PMN and MNC. These findings demonstrate that the production of sTLR2 seems unaffected by those stimulations. Only MNC is down- regulated by those stimulations in sCD14 expression. Likely sTLR2 is an existed molecule in normal serum and sCD14 is related to the immunity in SLE. Although further studies elucidating the detailed mechanisms of sTLR2 and sCD14 are required, this study provides a new direction for SLE treatment and prevention.