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Infection and Immunity, November 2000, p. 6209-6214, Vol. 68, No. 11
Department of Microbiology and Immunology and
Division of Bacterial Toxins, Research Center for Infectious Diseases,
Aichi Medical University, Nagakute, Aichi 480-1195, Japan
Received 13 March 2000/Returned for modification 10 July
2000/Accepted 11 August 2000
The effect of gamma interferon (IFN-
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Augmentation of Nitric Oxide Production by Gamma
Interferon in a Mouse Vascular Endothelial Cell Line and Its Modulation
by Tumor Necrosis Factor Alpha and Lipopolysaccharide
), tumor necrosis factor
alpha (TNF-
), and lipopolysaccharide (LPS) on nitric oxide (NO)
production in the mouse vascular aortic endothelial cell line END-D was
examined. LPS, TNF-
, and a low concentration of IFN-
inhibited NO
production in END-D cells, while a high concentration of IFN-
definitely enhanced it. The NO production induced by a high
concentration of IFN-
was further augmented by using IFN-
in
combination with LPS or TNF-
. In sequential incubations of LPS and
IFN-
, the enhancement of NO production required prior treatment with
IFN-
. Stimulation of END-D cells with a high concentration of
IFN-
led to the expression of inducible NO synthase (iNOS). The
augmentation of NO production by IFN-
alone or in combination with
LPS or TNF-
was completely blocked by several inhibitors of iNOS. It
was strongly suggested that a high concentration of IFN-
itself
enhanced NO production in END-D cells through inducing the expression
of iNOS. LPS and TNF-
exclusively modulated the activity of iNOS
once its expression was triggered by IFN-
. On the other hand, a low
concentration of IFN-
, LPS, and TNF-
reduced NO production
through down-regulating constitutive NOS (cNOS). The differential
regulation of cNOS- and iNOS-mediated NO production by IFN-
,
TNF-
, and LPS is discussed.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan. Phone: 81-561-62-3311, ext. 2269. Fax: 81-561-63-9187. E-mail: yokochi{at}aichi-med-u.ac.jp.
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