Differing effects of aprotinin and ε-aminocaproic acid on cytokine-induced inducible nitric oxide synthase expression

Gary E. Hill, Janice A. Taylor, Richard A. Robbins

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background. Cell expression of inducible nitric oxide synthase (iNOS) is increased by cytokines, resulting in high endogenous levels of nitric oxide. Expression of iNOS has been implicated in organ injury, including myocardial reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease inhibitors aprotinin and ε-aminocaproic acid (EACA), used to reduce blood loss after cardiac operations, were evaluated in vitro on cytokine-induced iNOS expression and nitric oxide production. Methods. A murine bronchial epithelial cell line was stimulated with a mixture of cytokines (tumor necrosis factor-α, interleukin-1β, and interferon-γ) with or without aprotinin or EACA. The resultant iNOS expression was measured by northern blot analysis, and nitric oxide production was assessed by cell supernatant nitrite levels. Results. Nitrite concentrations in the supernatant were significantly increased after cytokine stimulation; they were not affected by any concentration of EACA but were significantly (p < 0.05) reduced by aprotinin. Aprotinin significantly (p < 0.05) reduced cytokine-induced iNOS expression, whereas EACA had no effect. Conclusions. Aprotinin, but not EACA, reduces cytokine-induced nitric oxide production by inhibition of iNOS expression. Because increased endogenous nitric oxide levels secondary to iNOS activation have been implicated in organ injury, aprotinin may have clinical benefit compared with EACA when used for cardiac operations.

Original languageEnglish (US)
Pages (from-to)74-77
Number of pages4
JournalAnnals of Thoracic Surgery
Volume63
Issue number1
DOIs
StatePublished - Jan 1997

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Aminocaproic Acid
Aprotinin
Nitric Oxide Synthase Type II
Cytokines
Nitric Oxide
Nitrites
Myocardial Reperfusion Injury
Serine Proteinase Inhibitors
Wounds and Injuries
Protease Inhibitors
Interleukin-1
Northern Blotting
Interferons
Tumor Necrosis Factor-alpha
Epithelial Cells
Cell Line

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Differing effects of aprotinin and ε-aminocaproic acid on cytokine-induced inducible nitric oxide synthase expression. / Hill, Gary E.; Taylor, Janice A.; Robbins, Richard A.

In: Annals of Thoracic Surgery, Vol. 63, No. 1, 01.1997, p. 74-77.

Research output: Contribution to journalArticle

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AB - Background. Cell expression of inducible nitric oxide synthase (iNOS) is increased by cytokines, resulting in high endogenous levels of nitric oxide. Expression of iNOS has been implicated in organ injury, including myocardial reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease inhibitors aprotinin and ε-aminocaproic acid (EACA), used to reduce blood loss after cardiac operations, were evaluated in vitro on cytokine-induced iNOS expression and nitric oxide production. Methods. A murine bronchial epithelial cell line was stimulated with a mixture of cytokines (tumor necrosis factor-α, interleukin-1β, and interferon-γ) with or without aprotinin or EACA. The resultant iNOS expression was measured by northern blot analysis, and nitric oxide production was assessed by cell supernatant nitrite levels. Results. Nitrite concentrations in the supernatant were significantly increased after cytokine stimulation; they were not affected by any concentration of EACA but were significantly (p < 0.05) reduced by aprotinin. Aprotinin significantly (p < 0.05) reduced cytokine-induced iNOS expression, whereas EACA had no effect. Conclusions. Aprotinin, but not EACA, reduces cytokine-induced nitric oxide production by inhibition of iNOS expression. Because increased endogenous nitric oxide levels secondary to iNOS activation have been implicated in organ injury, aprotinin may have clinical benefit compared with EACA when used for cardiac operations.

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