鋰鹽和丙戊酸對於樹突狀細胞的免疫調控以及對小鼠關節炎疾病模式的影響

The effect of lithium and valproic acid on the function of dendritic cells and mouse collagen-induced arthritis

鄭傑宇(Jye-Yu Jenq)

指導教授 ： 呂思潔

臺北醫學大學/醫學院/醫學科學研究所/碩士(2012年)

https://doi.org/10.6831/TMU.2012.00044

摘要

無資料

關鍵字

鋰鹽 ； 丙戊酸 ； 樹突細胞 ； 小鼠關節炎

並列摘要

Lithium (LiCl) and valproic acid (VPA) have been chosen as the first line medicine for bipolar disorder (BD). According to previous researches, patients with BD have been reported to have altered immune functions, for example hyperthyroidism, pancreatic islets or gastric mucosa autoimmune diseases. Patients treated with LiCl and VPA modulate immune status. LiCl stabilize the emotion and have neuroprotective effect by inhibit glycogen synthase kinase 3β (GSK-3β) pathway. VPA may modulate immune system by inhibit histone deacetylase and down-regulate NF-κB expression, and decrease pro- inflammatory cytokines secretion in patients of BD. We hypothesized that LiCl and VPA may have immunomodulaty function on dendritic cells and combined treatment with LiCl and VPA may have additive effects. First, we investigated in the effect of LiCl and VPA on the functions of dendritic cells (DCs) in vitro. Human peripheral blood mononuclear cell (PBMC) derived DCs were generated and treated with LiCl and VPA for the examination of DC functions. Our results shown LiCl significantly increased the expression of CD86 and CD83 on iDCs to 2 folds as compared to control, and significantly decreased the expression of CD1a. VPA significantly decreased the expression of CD1a. Combined treatment with LiCl and VPA further decreased the expression of CD1a. LPS-activated mature DCs were treated with LiCl and VPA for examination of surface molecules. Cotreatment LiCl and VPA significantly decreased the expression of CD14. Level of interleukin-6 (IL-6) is significantly decreased by cotreatment with LiCl and VPA in mature dendritic cells. These data suggest that LiCl and VPA might have additive effects in decreased the CD1a expression and IL-6 secretion. Furthormore, mouse type II collagen-induced arthritis (CIA) model were established successfully. Our results show oral treatment with LiCl and VPA in CIA mouse decreased inflammatory scores and feet thickness. Combined treatment with LiCl and VPA have significantly effect on CIA mouse. These data suggest that Combined treatment with LiCl and VPA have additive effects on DC functions and on CIA model.

並列關鍵字

lithium ； valproic acid ； dendritic cell ； collagen-induced arthritis

參考文獻

1. Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL: The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. The American Journal of Human Genetics 2002, 71(3):651-655.

2. Liu HC, Yang YY, Chou YM, Chen KP, Shen WW, Leu SJ: Immunologic variables in acute mania of bipolar disorder. Journal of neuroimmunology 2004, 150(1):116-122.

3. Cassidy F, Wilson WH, Carroll BJ: Leukocytosis and hypoalbuminemia in mixed bipolar states: evidence for immune activation. Acta Psychiatrica Scandinavica 2002, 105(1):60-64.

4. Phiel CJ, Klein PS: Molecular targets of lithium action. Annual review of pharmacology and toxicology 2001, 41(1):789-813.

5. Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME: Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997, 275(5300):661-665.