Regulation of gene expression and nitric oxide production in murine macrophages by the serine/threonine phosphatase inhibitor okadaic acid

S. A. Barber, C. A. Salkowski, M. J. Fultz, P. Y. Perera, R. McNally, S. N. Vogel

Research output: Contribution to journalArticle

Abstract

LPS-stimulated macrophages produce cytokines which, at appropriate levels, direct successful immune responses against harmful pathogens. However, excessive cytokine production, as seen in endotoxemia, results in pathophysiological damage to the host. Therefore, understanding mechanisms of cytokine regulation may aid the development of strategies designed to control cytokine production during an ongoing immune response. We have examined the role of okadaic acid-sensitive phosphatases in the production of cytokines and nitric oxide by macrophages. Okadaic acid induces TNFα, IL-1β, IL-6, IFN-β, and IP-10, but not IL-10 or IL-12 (p40) mRNA. Okadaic acid differentially regulates the expression of LPS-inducible IL-10 and IL-12 (p40) mRNA. These findings suggest that okadaic acid-sensitive phosphatases are key regulators of cytokine production in unstimulated and immune-activated macrophages. Finally, okadaic acid inhibits iNOS mRNA and nitric oxide production by macrophages activated by LPS and IFN-γ.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalInnate Immunity
Volume3
Issue number1
DOIs
StatePublished - 1996

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Okadaic Acid
Phosphoprotein Phosphatases
Gene Expression Regulation
Nitric Oxide
Macrophages
Cytokines
Interleukin-12
Interleukin-10
Messenger RNA
Endotoxemia
Interleukin-1
Interleukin-6

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Immunology
  • Microbiology
  • Infectious Diseases

Cite this

Regulation of gene expression and nitric oxide production in murine macrophages by the serine/threonine phosphatase inhibitor okadaic acid. / Barber, S. A.; Salkowski, C. A.; Fultz, M. J.; Perera, P. Y.; McNally, R.; Vogel, S. N.

In: Innate Immunity, Vol. 3, No. 1, 1996, p. 19-27.

Research output: Contribution to journalArticle

Barber, S. A. ; Salkowski, C. A. ; Fultz, M. J. ; Perera, P. Y. ; McNally, R. ; Vogel, S. N. / Regulation of gene expression and nitric oxide production in murine macrophages by the serine/threonine phosphatase inhibitor okadaic acid. In: Innate Immunity. 1996 ; Vol. 3, No. 1. pp. 19-27.
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