Tumor necrosis factor α acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytes

2007 ◽  
Vol 56 (2) ◽  
pp. 464-475 ◽  
Author(s):  
Yohei Kirino ◽  
Mitsuhiro Takeno ◽  
Shuji Murakami ◽  
Masayoshi Kobayashi ◽  
Hideo Kobayashi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Heme Oxygenase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inflammatory Responses ◽  
Heme Oxygenase 1 ◽  
Factor Α ◽  
Necrosis Factor

Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts

2000 ◽  
Vol 278 (2) ◽  
pp. L312-L319 ◽  
Author(s):  
Irina Petrache ◽  
Leo E. Otterbein ◽  
Jawed Alam ◽  
Gordon W. Wiegand ◽  
Augustine M. K. Choi
Keyword(s):  
Carbon Monoxide ◽  
Tumor Necrosis Factor ◽  
Heme Oxygenase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Heme Oxygenase 1 ◽  
Cultured Fibroblasts ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts of biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, the induction of which is associated with protection against oxidative stress. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or more of the catalytic by-products provide antioxidant functions either directly or indirectly. The involvement of reactive oxygen species in apoptosis raised the question of a possible role for HO-1 in programmed cell death. Using the tetracycline-regulated expression system, we show here that conditional overexpression of HO-1 prevents tumor necrosis factor-α-induced apoptosis in murine L929 fibroblasts. Inhibition of apoptosis was not observed in the presence of tin protoporphyrin, a specific inhibitor of HO activity, and in cells overexpressing antisense HO-1. Interestingly, exogenous administration of a low concentration of carbon monoxide also prevented tumor necrosis factor-α-induced apoptosis in L929 fibroblasts. Inhibition of tumor necrosis factor-α-induced apoptosis by HO-1 overexpression was reversed by 1 H-(1,2,4)oxadiazolo(4,3- a)quinoxalin-1-one, an inhibitor of guanylate cyclase, which is a target enzyme for carbon monoxide. Taken together, our data suggest that the antiapoptotic effect of HO-1 may be mediated via carbon monoxide.

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

1998 ◽  
Vol 274 (3) ◽  
pp. H883-H891 ◽  
Author(s):  
Christi M. Terry ◽  
Jennifer A. Clikeman ◽  
John R. Hoidal ◽  
Karleen S. Callahan
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Heme Oxygenase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Heme Oxygenase 1 ◽  
Human Endothelial Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

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.

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