The suppression of T cell function and NF Kappa B expression by serine protease inhibitors is blocked by N-acetylcysteine
Direct evidence that N-acetylcysteine (NAC) enhances the immune response of peripheral blood T cells at the level of NF Kappa B is presented. In addition, NAC blocks the suppression of T cell mitogenesis and cytokine production by protease inhibitors such as N-tosylphenylalanine chloromethyl ketone...
Saved in:
Published in | Cellular immunology Vol. 173; no. 1; pp. 124 - 130 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
10.10.1996
|
Online Access | Get full text |
Cover
Loading…
Summary: | Direct evidence that N-acetylcysteine (NAC) enhances the immune response of peripheral blood T cells at the level of NF Kappa B is presented. In addition, NAC blocks the suppression of T cell mitogenesis and cytokine production by protease inhibitors such as N-tosylphenylalanine chloromethyl ketone (TPCK). The proliferative responses of purified CD4 super(+) or CD8 super(+) T cells are suppressed more strongly by TPCK when anti-CD28 rather than the phorbol ester PMA is used as the mitogenic coactivator. Cytokine (IL-2, IL-6, INF- gamma ) production is inhibited 95-100% by concentrations of TPCK that totally suppress the mitogenesis of CD4 super(+) or CD8 super(+) cells. Using electrophoretic mobility shift assays, we find that TPCK virtually abolishes (to less than 1%) the levels of NF Kappa B (but not Oct-1) found in nuclear and whole cell extracts of activated T cells. Strikingly, the immunosuppressive effects of TPCK are blocked when T cells are pretreated for 15 min with 5 mM NAC. NAC not only blocks the effect of TPCK but enhances mitogenesis and cytokine production (>2.5-fold in some cases) upon activation of unsuppressed T cells. Our data support the notion that NF Kappa B and I Kappa B proteases play obligate roles in T cell activation and mitogenesis, roles that are enhanced significantly by NAC. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0008-8749 |
DOI: | 10.1006/cimm.1996.0258 |