The inhibitory role of lactacystin and beta-lactacystin on T-cell activation and proliferation

Acta Biochim Biophys Sin (Shanghai). 2004 Feb;36(2):123-7. doi: 10.1093/abbs/36.2.123.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology*
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • CD3 Complex / biosynthesis
  • Cell Division
  • Cysteine Proteinase Inhibitors / pharmacology
  • Down-Regulation
  • Flow Cytometry
  • Humans
  • Interleukin-2 / metabolism
  • Lectins, C-Type
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Muscle Proteins / metabolism
  • Proteasome Endopeptidase Complex
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / metabolism*
  • Time Factors

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Cysteine Proteinase Inhibitors
  • Interleukin-2
  • Lectins, C-Type
  • Muscle Proteins
  • PSME1 protein, human
  • Proteins
  • RNA, Messenger
  • Receptors, Interleukin-2
  • lactacystin beta-lactone
  • lactacystin
  • Proteasome Endopeptidase Complex
  • Acetylcysteine