Suppression of TNF-α gene expression by hemin: Implications for the role of iron homeostasis in host inflammatory responses

Abstract

Tumor necrosis factor a (TNF-α) has multiple effects on iron homeostasis and erythropoiesis and has been implicated in the pathogenesis of the anemia of inflammation. We postulated that intracellular iron in turn may regulate the expression of TNF-α. In the human monocytic leukemia cell line, THP-1, low basal TNF-α message levels were stimulated (sevenfold) when serum was excluded from the culture medium. Addition of heroin completely suppressed TNF-α expression. Similarly, hemin suppressed lipopolysaccharide- induced expression of TNF-α. Sn-protoporphyrin, an inhibitor of heme oxygenase (which releases iron from hemin), prevented hemin-induced suppression of TNF-α expression. Conversely, the intracellular iron chelator, desferrioxamine, stimulated TNF-α expression. Thus, the expression of TNF-α, itself a physiological regulator of iron homeostasis, appears to be controlled by intracellular levels of iron.