Proteasome participates in the alteration of signal transduction in T and B lymphocytes following trauma-hemorrhage

T. S.Anantha Samy, Martin G. Schwacha, Chun Shiang Chung, William G. Cioffi, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Proteasomes are essential components of the cellular protein degradation machinery. They are nonlysosomal and their participation is critical for (1) the removal of short lived proteins involved in metabolic regulation and cell proliferation, (2) the control of the activities of regulators involved in gene transcription, such as nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT1), and (3) processing of antigenic peptides for MHC class I presentation. Trauma-hemorrhage induces profound immunosuppression which is characterized by reduced splenocyte proliferation, interleukin (IL)-2 and interferon (IFN)-γ productive capacity, increased activation of transcription factors NF-κB and STAT1 in splenic T lymphocytes, reduced macrophage antigen presentation capacity and inordinate release of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-α. Furthermore, it appears that the activity of several regulatory proteins involved in immune function is altered by trauma-hemorrhage. Since proteasomes are involved in regulation and removal of regulatory proteins, we hypothesized that trauma-hemorrhage alters proteasomal activity in splenic lymphocytes. The data showed that activities of 26s proteasome from CD3+CD4+ and CD3+CD8+ splenic T lymphocytes were enhanced following trauma-hemorrhage which was associated with increased expression of NF-κB and STAT1. On the other hand, trauma-hemorrhage attenuated the activity of 26s proteasome from splenic B lymphocytes which was restored upon IFN-γ stimulation and correlated with increased expression of NF-κB. These studies indicate a potential role for proteasomes in the regulation of signal transduction in splenic T and B lymphocytes following trauma-hemorrhage, and also suggest them as potential therapeutic targets for attenuation of immune suppression associated with this form of injury. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)92-104
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1453
Issue number1
DOIs
StatePublished - Jan 6 1999

Keywords

  • JAK1
  • Nuclear factor-κB
  • Proteasome
  • Signal transducer and activator of transcription
  • Splenic lymphocyte
  • Trauma-hemorrhage

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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