Lymphocyte proliferation and activation induced cell death in model of primary biliary cirrhosis
10.3760/cma.j.issn.0254-1432.2010.04.001
- VernacularTitle:原发性胆汁性肝硬化模型中淋巴细胞增殖及活化诱导凋亡机制研究
- Author:
Tingwang JIANG
;
Huaimin XIONG
;
Jianhua SHENG
;
Yanping GONG
;
Yanhong SHEN
;
Jianwen LU
;
Guohua XU
;
Anmei DENG
;
Renqian ZHONG
- Publication Type:Journal Article
- Keywords:
Primary biliary cirrhosis;
Apoptosis;
Immune tolerance;
FLIP_L;
Caspase-8
- From:
Chinese Journal of Digestion
2010;30(4):217-221
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the immune tolerance in animal models of primary biliary cirrhosis (PBC) by determining the cell proliferation and activation induced cell death (AICD).Methods C57BL/6 mice were injected with 5 mg/kg of polyI:C to develope PBC models. The lymphocytes and CD4~+ T cells were separated from spleens and livers 16 weeks later and were stimulated by M2, conA and anti-CD3 for cell proliferation and AICD. Expression of apoptosis related genes and proteins were detected by real time polymerase chain reaction (PCR) and Western blotting, respectively. Results ① The lymphocyte proliferation was 0.1988 ± 0.0111 in blank controls and 0. 2068±0. 0115 in PBS treated mice with no significant difference (P>0.05). However, an abundant lymphocyte proliferation was found in PBC mice (0. 358 ± 0. 022), which was higher than that in controls and PBS treated mice. The proliferation of lymphocyte from liver was greater than that from spleen in PBC mice (P<0.01). ② The apoptotic rate in blank controls (74.70%±4.58%) and PBS treated mice (74.20%±4.44%) was higher than that in PBC mice (44.85%±6.47%,P<0.01),but no difference was found between blank controls and PBS treated mice (P>0.05). Furthermore, the apoptosis rate of T cells from livers were significantly lower than that from spleens in PBC mice (P<0.01). ③ The expressions of FasL and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in PBC mice were lower than those in PBS treated mice (P<0. 01), but there was no change in expression of Fas was found. ④ The expression of Fas-associated death domain-like interleukin-1-β-converting enzyme-inhibitory protein (FLIP_L) in PBC mice was higher than that in blank controls. Moreover, the expression of FLIP_L in livers was higher than that in spleens in PBC mice (P<0. 01). Conclusios The elevated expression of FLIP_L may inhibit AICD. Besides, the decreased expressions of FasL and TRAIL may also help in the enhancement of the anti-apoptotic ability in lymphocytes and in the aggravation of portal area inflammation.
