Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides

Thomas W. Redford, Ae-Kyung Yi, Courtney T. Ward, Arthur M. Krieg

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Certain sequences of nucleotides (CpG motifs) in bacterial DNA or synthetic oligonucleotides (CpG DNA) promote the production of proinflammatory cytokines, including TNF-α, IFN-γ, IL-6, and IL-12. Here we demonstrate that the immunosuppressant cyclosporin A (CsA) unexpectedly enhanced CpG DNA-induced IL-12 production in murine splenocytes. CsA did not inhibit CpG DNA-induced TNF-α or IL-6 production, but decreased the production of IFN-γ by CpG DNA. Upon examining mechanisms by which CsA increases IL-12 production, we found that CpG DNA can also induce IL-10 production in B cells and that this production was sensitive to CsA. IL-10 has anti-inflammatory effects and can reduce the production of IL-12. To determine the possible role of CsA-modulated IL-10 production in mediating the increased IL-12 levels, splenocytes from IL-10 gene-disrupted mice (IL- 10 -/-) and splenocytes cultured in anti-IL-10 Ab were studied. CpG DNA- stimulated IL-10 (-/-) splenocytes demonstrated no increase in IL-12 levels in the presence of CsA. Anti-IL-10 Ab treatment of normal splenocytes increased the magnitude of CpG DNA-induced IL-12 production to that seen with CsA. These results suggest that CpG DNA induces CsA-sensitive IL-10 production in B cells and that IL-10 acts as a negative feedback regulator of CpG DNA-induced IL-12 production.

Original languageEnglish (US)
Pages (from-to)3930-3935
Number of pages6
JournalJournal of Immunology
Volume161
Issue number8
StatePublished - Oct 15 1998
Externally publishedYes

Fingerprint

Bacterial DNA
Oligodeoxyribonucleotides
Interleukin-12
Interleukin-10
Cyclosporine
DNA
Interleukin-6
B-Lymphocytes
Nucleotide Motifs
Immunosuppressive Agents
Oligonucleotides
Anti-Inflammatory Agents
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides. / Redford, Thomas W.; Yi, Ae-Kyung; Ward, Courtney T.; Krieg, Arthur M.

In: Journal of Immunology, Vol. 161, No. 8, 15.10.1998, p. 3930-3935.

Research output: Contribution to journalArticle

Redford, Thomas W. ; Yi, Ae-Kyung ; Ward, Courtney T. ; Krieg, Arthur M. / Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides. In: Journal of Immunology. 1998 ; Vol. 161, No. 8. pp. 3930-3935.
@article{3cc34d8caf9141789b0db833a0845ef5,
title = "Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides",
abstract = "Certain sequences of nucleotides (CpG motifs) in bacterial DNA or synthetic oligonucleotides (CpG DNA) promote the production of proinflammatory cytokines, including TNF-α, IFN-γ, IL-6, and IL-12. Here we demonstrate that the immunosuppressant cyclosporin A (CsA) unexpectedly enhanced CpG DNA-induced IL-12 production in murine splenocytes. CsA did not inhibit CpG DNA-induced TNF-α or IL-6 production, but decreased the production of IFN-γ by CpG DNA. Upon examining mechanisms by which CsA increases IL-12 production, we found that CpG DNA can also induce IL-10 production in B cells and that this production was sensitive to CsA. IL-10 has anti-inflammatory effects and can reduce the production of IL-12. To determine the possible role of CsA-modulated IL-10 production in mediating the increased IL-12 levels, splenocytes from IL-10 gene-disrupted mice (IL- 10 -/-) and splenocytes cultured in anti-IL-10 Ab were studied. CpG DNA- stimulated IL-10 (-/-) splenocytes demonstrated no increase in IL-12 levels in the presence of CsA. Anti-IL-10 Ab treatment of normal splenocytes increased the magnitude of CpG DNA-induced IL-12 production to that seen with CsA. These results suggest that CpG DNA induces CsA-sensitive IL-10 production in B cells and that IL-10 acts as a negative feedback regulator of CpG DNA-induced IL-12 production.",
author = "Redford, {Thomas W.} and Ae-Kyung Yi and Ward, {Courtney T.} and Krieg, {Arthur M.}",
year = "1998",
month = "10",
day = "15",
language = "English (US)",
volume = "161",
pages = "3930--3935",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides

AU - Redford, Thomas W.

AU - Yi, Ae-Kyung

AU - Ward, Courtney T.

AU - Krieg, Arthur M.

PY - 1998/10/15

Y1 - 1998/10/15

N2 - Certain sequences of nucleotides (CpG motifs) in bacterial DNA or synthetic oligonucleotides (CpG DNA) promote the production of proinflammatory cytokines, including TNF-α, IFN-γ, IL-6, and IL-12. Here we demonstrate that the immunosuppressant cyclosporin A (CsA) unexpectedly enhanced CpG DNA-induced IL-12 production in murine splenocytes. CsA did not inhibit CpG DNA-induced TNF-α or IL-6 production, but decreased the production of IFN-γ by CpG DNA. Upon examining mechanisms by which CsA increases IL-12 production, we found that CpG DNA can also induce IL-10 production in B cells and that this production was sensitive to CsA. IL-10 has anti-inflammatory effects and can reduce the production of IL-12. To determine the possible role of CsA-modulated IL-10 production in mediating the increased IL-12 levels, splenocytes from IL-10 gene-disrupted mice (IL- 10 -/-) and splenocytes cultured in anti-IL-10 Ab were studied. CpG DNA- stimulated IL-10 (-/-) splenocytes demonstrated no increase in IL-12 levels in the presence of CsA. Anti-IL-10 Ab treatment of normal splenocytes increased the magnitude of CpG DNA-induced IL-12 production to that seen with CsA. These results suggest that CpG DNA induces CsA-sensitive IL-10 production in B cells and that IL-10 acts as a negative feedback regulator of CpG DNA-induced IL-12 production.

AB - Certain sequences of nucleotides (CpG motifs) in bacterial DNA or synthetic oligonucleotides (CpG DNA) promote the production of proinflammatory cytokines, including TNF-α, IFN-γ, IL-6, and IL-12. Here we demonstrate that the immunosuppressant cyclosporin A (CsA) unexpectedly enhanced CpG DNA-induced IL-12 production in murine splenocytes. CsA did not inhibit CpG DNA-induced TNF-α or IL-6 production, but decreased the production of IFN-γ by CpG DNA. Upon examining mechanisms by which CsA increases IL-12 production, we found that CpG DNA can also induce IL-10 production in B cells and that this production was sensitive to CsA. IL-10 has anti-inflammatory effects and can reduce the production of IL-12. To determine the possible role of CsA-modulated IL-10 production in mediating the increased IL-12 levels, splenocytes from IL-10 gene-disrupted mice (IL- 10 -/-) and splenocytes cultured in anti-IL-10 Ab were studied. CpG DNA- stimulated IL-10 (-/-) splenocytes demonstrated no increase in IL-12 levels in the presence of CsA. Anti-IL-10 Ab treatment of normal splenocytes increased the magnitude of CpG DNA-induced IL-12 production to that seen with CsA. These results suggest that CpG DNA induces CsA-sensitive IL-10 production in B cells and that IL-10 acts as a negative feedback regulator of CpG DNA-induced IL-12 production.

UR - http://www.scopus.com/inward/record.url?scp=0032532309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032532309&partnerID=8YFLogxK

M3 - Article

VL - 161

SP - 3930

EP - 3935

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -