| Summary: | 博士 === 國立中興大學 === 生物科技學研究所 === 104 === In the first part of thesis, we investigated whether long-term exposure to environmental heavy metals is associated with worsened rheumatoid arthritis (RA). Previous studies indicated correlations exist between heavy metals and RA disease activities; however, these studies failed to address environmental pollution as a source of metal intake.
Heavy metal pollution in farmland at Changhua County is a great concern and has already exerted a negative effect on the health of local people. We found that RA patients living where farm soils contained high levels of copper had increased disease activities. Moreover, in vitro and in vivo studies showed that copper can promote activation of splenocytes and macrophages, and increase arthritis scores in mice with collagen-induced arthritis (CIA). These findings support that copper is a heavy metal correlated with inflammation in RA. Chronic exposure to copper from the environment can aggravate RA.
Tryptophan is an essential amino acid for humans. It has two major metabolic pathways: the kynurenine pathway and serotonin pathway. 5-hydroxytryptophan (5-HTP) is an intermediate in serotonin synthesis. In certain countries, 5-HTP is used as a dietary supplement to improve depression and appetite. Previous studies found that 5-HTP can suppress immune responses, thus prompted us to investigate the effects of 5-HTP on CIA mice.
In the second part of thesis, we provide evidence that 5-HTP can inhibit the development of Th1 and Th17 cells and decrease the production of proinflammatory mediators in activated splenocytes. In addition, supplement of 5-HTP prevented the development of CIA in mice. These findings imply 5-HTP may be an option for prevention of human RA.
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