,The Inhibitory Role of Lactacystin and β-Lactacystin on T-cell Activation and Proliferation

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To evaluate the effects of proteasome inhibitors lactacystin (LAC) and β-lactacystin (β-LAC)on the proliferation and activation of T lymphocytes, flow cytometry was used to analyze the proliferationand the expression of CD69, CD25 and CD3 of T lymphocytes activated by PHA. Furthermore, theexpressions of PA28 and IL-2 mRNA were assayed by competitive RT-PCR. The results indicated that:(1) LAC and β-LAC significantly decreased the incorporation of BrdU and inhibited T lymphocytesproliferation in T lymphocytes activated by PHA; (2) although LAC and β-LAC did not affect the expressionof CD69 at any time, they significantly inhibited the expression of CD25 (48h, 72h, P<0.05);(3) in comparison with control, LAC and β-LAC significantly down-regulated the expression of PA28and IL-2 mRNA (48h, 72h, P<0.05). LAC and β-LAC significantly inhibited the proliferation and activationof T cells. Mechanisms involved are inhibition of CD25 and down-regulation of PA28 and IL-2 mRNAexpressions.
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