Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle.

D. K. Nakayama, D. A. Geller, C. J. Lowenstein, H. D. Chern, P. Davies, B. R. Pitt, R. L. Simmons, T. R. Billiar

Research output: Contribution to journalArticle

Abstract

In the current study, we describe cytokine and Escherichia coli lipopolysaccharide (LPS) induction of nitric oxide (NO) synthase mRNA levels in cultured smooth muscle from rat pulmonary artery (RPASM). Exposure of RPASM to interleukin-1 beta, interferon-gamma, or LPS alone did not significantly affect NO synthesis, as determined by nitrite concentrations in media. Exposure to tumor necrosis factor-alpha caused a modest (2x) increase in nitrite production. In contrast, exposure to a combination of the above three cytokines and LPS caused a large increase in NO synthesis. Exposure of RPASM to this combination caused an increase in mRNA levels of NO synthase (as described by Northern blot analysis with 32P-cDNA probe to an inducible form of NO synthase present in murine macrophages) that was apparent as early as 4 h. Expression of the induced gene product after exposure to the cytokine and LPS mixture was evident by significant increases in nitrite production at 12 h. Production of nitrite was completely abolished in the presence of NG-monomethyl-L-arginine (NMA), and this inhibition was reversible by the addition of excess L-arginine. NO synthase mRNA levels were not affected by NMA. The nitrite production induced by the combination of cytokines and LPS was abolished by pretreating cells with cycloheximide. These data indicate that a combination of cytokines and LPS affect expression of the gene for the inducible form of NO synthase in cultured RPASM.

Original languageEnglish (US)
Pages (from-to)471-476
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume7
Issue number5
StatePublished - Nov 1992
Externally publishedYes

Fingerprint

Nitric Oxide Synthase
Pulmonary Artery
Smooth Muscle
Lipopolysaccharides
Muscle
Rats
Nitrites
Cytokines
omega-N-Methylarginine
Nitric Oxide Synthase Type II
Messenger RNA
Nitric Oxide
Genes
Gene Expression
Macrophages
Interferon-beta
Cycloheximide
Interleukin-1beta
Northern Blotting
Escherichia coli

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Nakayama, D. K., Geller, D. A., Lowenstein, C. J., Chern, H. D., Davies, P., Pitt, B. R., ... Billiar, T. R. (1992). Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle. American Journal of Respiratory Cell and Molecular Biology, 7(5), 471-476.

Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle. / Nakayama, D. K.; Geller, D. A.; Lowenstein, C. J.; Chern, H. D.; Davies, P.; Pitt, B. R.; Simmons, R. L.; Billiar, T. R.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 7, No. 5, 11.1992, p. 471-476.

Research output: Contribution to journalArticle

Nakayama, DK, Geller, DA, Lowenstein, CJ, Chern, HD, Davies, P, Pitt, BR, Simmons, RL & Billiar, TR 1992, 'Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle.', American Journal of Respiratory Cell and Molecular Biology, vol. 7, no. 5, pp. 471-476.
Nakayama, D. K. ; Geller, D. A. ; Lowenstein, C. J. ; Chern, H. D. ; Davies, P. ; Pitt, B. R. ; Simmons, R. L. ; Billiar, T. R. / Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat pulmonary artery smooth muscle. In: American Journal of Respiratory Cell and Molecular Biology. 1992 ; Vol. 7, No. 5. pp. 471-476.
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