Comparison of tumor necrosis factor-alpha effect on the expression of iNOSin macrophage and cardiac myocytes

Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha ), are elevated during cardiopulmonary bypass (CPB), heart failure, and inf lammatory cardiac and systemic diseases. Elevated TNF-alpha 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-alpha, which results in the induction of inducible nitric oxide synthase (iNOS) leading to a significant decline in cardiac fu nction and other direct effects. The hypothesis of this study was to determ ine if TNF-alpha would stimulate iNOS and its product nitric oxide (NO) sim ilarly in immortalized macrophage and cardiac myocytes. Cultured macrophage s (RAW 264.7) and cardiac myocytes (HL-1) were placed into two treatment gr oups and a control. The treatments included: (1) TNF-alpha and lipopolysacc haride (LPS); and (2) LPS, TNF-alpha, interleukin-1 beta (IL-1 beta) and in terferon-gamma (IFN-gamma) incubated for 8 h. The macrophage expression of iNOS increased by 365% (p < 0.01) and its product, NO, increased proportion ally. The expression of iNOS in the cardiac myocyte did not increase with T NF-<alpha> and LPS. However, with the addition of IFN-alpha and IL-1 beta i NOS increased to 140% of control (p< 0.05). Myocyte cGMP and NO did not inc rease significantly with TNF-<alpha> treatment. This study suggests that HL -1 myocyte iNOS cannot be induced by TNF-alpha, unlike macrophage iNOS. Fur thermore, the resultant cardiac dysfunction, secondary to proinflammatory c ytokines effects, is regulated via diverse pathways.