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ISSN 0582-9879 Acta Biochim et Biophysica Sinica 2004, 36(2):123-127 CN 31-1300/Q


The Inhibitory Role of Lactacystin and ¦Â-actacystin
on T-cell Activation and Proliferation

Peng-Hong SONG*, Hai-Yang XIE, Shu-Sen ZHENG, and Jian WU
( The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China )

Abstract To evaluate the effects of proteasome inhibitors lactacystin (LAC) and ¦Â-lactacystin (¦Â-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 ¦Â-LAC significantly decreased the incorporation of BrdU and inhibited T lymphocytes proliferation in T lymphocytes activated by PHA; (2) although LAC and ¦Â-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 ¦Â--LAC significantly down-regulated the expression of PA28 and IL-2 mRNA (48 h, 72 h, P<0.05). LAC and ¦Â-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.

Key words proteasome; T cells activation; immunosuppression

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Received: October 20, 2003 Accepted: December 8, 2003
This work was supported by a grant from the Doctoral Program Foundation of Education Ministry
*Corresponding author: Tel, 86-571-87236570; Fax, 86-571-87236570; E-mail, sph129@sina.com