Effect of tumor necrosis factor-α and interleukin-1α on heme oxygenase-1 expression in human endothelial cells

• Published in: American journal of physiology. Heart and circulatory physiology 1998-03, Vol.274 (3), p.H883-H891
• Main Authors: Terry, Christi M, Clikeman, Jennifer A, Hoidal, John R, Callahan, Karleen S
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.274.3.H883

Heme iron exacerbates oxidant damage by catalyzing the production of free radicals. Heme oxygenase is the rate-limiting enzyme involved in heme catabolism. An inducible form of heme oxygenase, heme oxygenase-1 (HO-1), is upregulated in oxidant and inflammatory settings, and recent work suggests that HO-1 induction may serve a protective function against oxidant injury. The ability of the endogenous inflammatory mediators, interleukin (IL)-1α, tumor necrosis factor-α (TNF-α), and IL-6, to enhance HO-1 expression in cultured human endothelial cells was examined in this study. HO-1 mRNA and protein expression were upregulated by IL-1α and TNF-α exposure but not by IL-6. Induction of HO-1 mRNA by IL-1α and TNF-α occurred in a concentration- and time-dependent fashion, with maximal expression occurring by 4 h for both cytokines. Induction depended on protein synthesis and occurred at the transcriptional level. Inhibition of the AP-1 transcription factor with curcumin decreased the cytokine induction of HO-1 mRNA, suggesting the involvement of this transcription factor in cytokine signaling of HO-1. The results of this study indicate that the endogenous inflammatory cytokines IL-1α and TNF-α induce HO-1 in endothelial cells, providing further evidence that HO-1 may be an important cellular response to inflammatory stress.