The Inhibitory Role of Lactacystin and β-Lactacystin on T-cell Activation and Proliferation
Abstract 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 proliferation and the expression of CD69, CD25 and CD3 of T lymphocytes activated by PHA. Furthermore, the expressions 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 lymphocytes proliferation in T lymphocytes activated by PHA; (2) although LAC and β-LAC did not affect the expression of CD69 at any time, they significantly inhibited the expression of CD25 (48 h, 72 h, P<0.05); (3) in comparison with control, LAC and β-LAC significantly down-regulated the expression of PA28 and IL-2 mRNA (48 h, 72 h, P<0.05). LAC and β-LAC significantly inhibited the proliferation and activation of T cells. Mechanisms involved are inhibition of CD25 and down-regulation of PA28 and IL-2 mRNA expressions.