Comparison of tumor necrosis factor-α effect on the expression of iNOS in macrophage and cardiac myocytes

D. Bradford Sanders, Douglas F. Larson, Kyler Hunter, Mark Gorman

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44 Scopus citations


Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), are elevated during cardiopulmonary bypass (CPB), heart failure, and inflammatory cardiac and systemic diseases. Elevated TNF-α has been linked to diminished cardiac function, decreased systemic vascular resistance, as well as renal and pulmonary dysfunction. It is understood that myocardial tissues can express TNF-α, which results in the induction of inducible nitric oxide synthase (iNOS) leading to a significant decline in cardiac function and other direct effects. The hypothesis of this study was to determine if TNF-α would stimulate iNOS and its product nitric oxide (NO) similarly in immortalized macrophage and cardiac myocytes. Cultured macrophages (RAW 264.7) and cardiac myocytes (HL-1) were placed into two treatment groups and a control. The treatments included: (1) TNF-α and lipopolysaccharide (LPS); and (2) LPS, TNF-α, interleukin-1β (IL-1β) and interferon-γ (IFN-γ) incubated for 8 h. The macrophage expression of iNOS increased by 365% (p < 0.01) and its product, NO, increased proportionally. The expression of iNOS in the cardiac myocyte did not increase with TNF-α and LPS. However, with the addition of IFN-α and IL-1β iNOS increased to 140% of control (p < 0.05). Myocyte cGMP and NO did not increase significantly with TNF-α treatment. This study suggests that HL-1 myocyte iNOS cannot be induced by TNF-α, unlike macrophage iNOS. Furthermore, the resultant cardiac dysfunction, secondary to proinflammatory cytokines effects, is regulated via diverse pathways.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
Issue number1
StatePublished - Jan 2001
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Safety Research
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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