NF-κB is involved in regulation of CD40 ligand expression on Mycobacterium bovis bacillus Calmette-Guérin-activated human T cells

Patricia Méndez-Samperio, Hilda Ayala, Abraham Vázquez

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Interaction between CD40L (CD154) on activated T cells and its receptor CD40 on antigen-presenting cells has been reported to be important in the resolution of infection by mycobacteria. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) up-regulates membrane expression of CD40L molecules is poorly understood. This study was done to investigate the role of the nuclear factor κB (NF-κB) signaling pathway in the regulation of CD40L expression in human CD4 + T cells stimulated with BCG. Specific pharmacologic inhibition of the NF-κB pathway revealed that this signaling cascade was required in the regulation of CD40L expression on the surface of BCG-activated CD4 + T cells. These results were further supported by the fact that treatment of BCG-activated CD4 + T cells with these pharmacological inhibitors significantly down-regulated CD40L mRNA. In this study, inhibitor κBα (IκBα) and IκBβ protein production was not affected by the chemical protease inhibitors and, more importantly, BCG led to the rapid but transient induction of NF-κB activity. Our results also indicated that CD40L expression on BCG-activated CD4 + T cells resulted from transcriptional up-regulation of the CD40L gene by a mechanism which is independent of de novo protein synthesis. Interestingly, BCG-induced activation of NF-κB and the increased CD40L cell surface expression were blocked by the protein kinase C (PKC) inhibitors 1-[5-isoquinolinesulfonyl]-2-methylpiperazine and salicylate, both of which block phosphorylation of IκB. Moreover, rottlerin a Ca 2+ -independent PKC isoform inhibitor, significantly down-regulated CD40L mRNA in BCG-activated CD4 + T cells. These data strongly suggest that CD40L expression by BCG-activated CD4 + T cells is regulated via the PKC pathway and by NF-κB DNA binding activity.
Original languageAmerican English
Pages (from-to)376-382
Number of pages7
JournalClinical and Diagnostic Laboratory Immunology
DOIs
StatePublished - 1 Jun 2003

Fingerprint

CD40 Ligand
T-cells
Bacilli
Mycobacterium bovis
Bacillus
T-Lymphocytes
Protein Kinase C
CD40 Antigens
Up-Regulation
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Messenger RNA
Mycobacterium Infections
Phosphorylation
Protein C Inhibitor
Salicylates
Antigen-Presenting Cells
Protein Kinase Inhibitors
T-Cell Antigen Receptor
Protease Inhibitors
Protein Isoforms

Cite this

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title = "NF-κB is involved in regulation of CD40 ligand expression on Mycobacterium bovis bacillus Calmette-Gu{\'e}rin-activated human T cells",
abstract = "Interaction between CD40L (CD154) on activated T cells and its receptor CD40 on antigen-presenting cells has been reported to be important in the resolution of infection by mycobacteria. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Gu{\'e}rin (BCG) up-regulates membrane expression of CD40L molecules is poorly understood. This study was done to investigate the role of the nuclear factor κB (NF-κB) signaling pathway in the regulation of CD40L expression in human CD4 + T cells stimulated with BCG. Specific pharmacologic inhibition of the NF-κB pathway revealed that this signaling cascade was required in the regulation of CD40L expression on the surface of BCG-activated CD4 + T cells. These results were further supported by the fact that treatment of BCG-activated CD4 + T cells with these pharmacological inhibitors significantly down-regulated CD40L mRNA. In this study, inhibitor κBα (IκBα) and IκBβ protein production was not affected by the chemical protease inhibitors and, more importantly, BCG led to the rapid but transient induction of NF-κB activity. Our results also indicated that CD40L expression on BCG-activated CD4 + T cells resulted from transcriptional up-regulation of the CD40L gene by a mechanism which is independent of de novo protein synthesis. Interestingly, BCG-induced activation of NF-κB and the increased CD40L cell surface expression were blocked by the protein kinase C (PKC) inhibitors 1-[5-isoquinolinesulfonyl]-2-methylpiperazine and salicylate, both of which block phosphorylation of IκB. Moreover, rottlerin a Ca 2+ -independent PKC isoform inhibitor, significantly down-regulated CD40L mRNA in BCG-activated CD4 + T cells. These data strongly suggest that CD40L expression by BCG-activated CD4 + T cells is regulated via the PKC pathway and by NF-κB DNA binding activity.",
author = "Patricia M{\'e}ndez-Samperio and Hilda Ayala and Abraham V{\'a}zquez",
year = "2003",
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doi = "10.1128/CDLI.10.3.376-382.2003",
language = "American English",
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journal = "Clinical and Diagnostic Laboratory Immunology",
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publisher = "American Society for Microbiology",

}

NF-κB is involved in regulation of CD40 ligand expression on Mycobacterium bovis bacillus Calmette-Guérin-activated human T cells. / Méndez-Samperio, Patricia; Ayala, Hilda; Vázquez, Abraham.

In: Clinical and Diagnostic Laboratory Immunology, 01.06.2003, p. 376-382.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - NF-κB is involved in regulation of CD40 ligand expression on Mycobacterium bovis bacillus Calmette-Guérin-activated human T cells

AU - Méndez-Samperio, Patricia

AU - Ayala, Hilda

AU - Vázquez, Abraham

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Interaction between CD40L (CD154) on activated T cells and its receptor CD40 on antigen-presenting cells has been reported to be important in the resolution of infection by mycobacteria. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) up-regulates membrane expression of CD40L molecules is poorly understood. This study was done to investigate the role of the nuclear factor κB (NF-κB) signaling pathway in the regulation of CD40L expression in human CD4 + T cells stimulated with BCG. Specific pharmacologic inhibition of the NF-κB pathway revealed that this signaling cascade was required in the regulation of CD40L expression on the surface of BCG-activated CD4 + T cells. These results were further supported by the fact that treatment of BCG-activated CD4 + T cells with these pharmacological inhibitors significantly down-regulated CD40L mRNA. In this study, inhibitor κBα (IκBα) and IκBβ protein production was not affected by the chemical protease inhibitors and, more importantly, BCG led to the rapid but transient induction of NF-κB activity. Our results also indicated that CD40L expression on BCG-activated CD4 + T cells resulted from transcriptional up-regulation of the CD40L gene by a mechanism which is independent of de novo protein synthesis. Interestingly, BCG-induced activation of NF-κB and the increased CD40L cell surface expression were blocked by the protein kinase C (PKC) inhibitors 1-[5-isoquinolinesulfonyl]-2-methylpiperazine and salicylate, both of which block phosphorylation of IκB. Moreover, rottlerin a Ca 2+ -independent PKC isoform inhibitor, significantly down-regulated CD40L mRNA in BCG-activated CD4 + T cells. These data strongly suggest that CD40L expression by BCG-activated CD4 + T cells is regulated via the PKC pathway and by NF-κB DNA binding activity.

AB - Interaction between CD40L (CD154) on activated T cells and its receptor CD40 on antigen-presenting cells has been reported to be important in the resolution of infection by mycobacteria. However, the mechanism(s) by which Mycobacterium bovis bacillus Calmette-Guérin (BCG) up-regulates membrane expression of CD40L molecules is poorly understood. This study was done to investigate the role of the nuclear factor κB (NF-κB) signaling pathway in the regulation of CD40L expression in human CD4 + T cells stimulated with BCG. Specific pharmacologic inhibition of the NF-κB pathway revealed that this signaling cascade was required in the regulation of CD40L expression on the surface of BCG-activated CD4 + T cells. These results were further supported by the fact that treatment of BCG-activated CD4 + T cells with these pharmacological inhibitors significantly down-regulated CD40L mRNA. In this study, inhibitor κBα (IκBα) and IκBβ protein production was not affected by the chemical protease inhibitors and, more importantly, BCG led to the rapid but transient induction of NF-κB activity. Our results also indicated that CD40L expression on BCG-activated CD4 + T cells resulted from transcriptional up-regulation of the CD40L gene by a mechanism which is independent of de novo protein synthesis. Interestingly, BCG-induced activation of NF-κB and the increased CD40L cell surface expression were blocked by the protein kinase C (PKC) inhibitors 1-[5-isoquinolinesulfonyl]-2-methylpiperazine and salicylate, both of which block phosphorylation of IκB. Moreover, rottlerin a Ca 2+ -independent PKC isoform inhibitor, significantly down-regulated CD40L mRNA in BCG-activated CD4 + T cells. These data strongly suggest that CD40L expression by BCG-activated CD4 + T cells is regulated via the PKC pathway and by NF-κB DNA binding activity.

U2 - 10.1128/CDLI.10.3.376-382.2003

DO - 10.1128/CDLI.10.3.376-382.2003

M3 - Article

SP - 376

EP - 382

JO - Clinical and Diagnostic Laboratory Immunology

JF - Clinical and Diagnostic Laboratory Immunology

SN - 1071-412X

ER -