Pharmacologic induction of heme oxygenase 1 reduces acute inflammatory arthritis in mice

Benallaoua, Mourad; François, Mathias; Batteux, Frédéric; Thelier, N.; Shyy, John Y.‐J.; Fitting, Catherine; Tsagris, Lydia; Boczkowski, Jorge; Savouret, Jean‐François; Corvol, Marie-Thérèse; Poiraudeau, Serge; Rannou, François

doi:10.1002/art.22749

Cited by 65 publications

(60 citation statements)

References 40 publications

(46 reference statements)

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“…Indeed, the generation of bilirubin, iron, and CO from HO activity can protect against cell death (21,64), and pharmacological induction of HO-1 is protective in a nonautoimmune arthritis mouse model (8). While modest HO-1 expression is cytoprotective, exacerbation of oxidative injury correlates with high HO-1 expression (37,66,67).…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione

Baglole

Sime²,

Phipps³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Baglole CJ, Sime PJ, Phipps RP. Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione. Am J Physiol Lung Cell Mol Physiol 295: L624 -L636, 2008. First published August 8, 2008 doi:10.1152/ajplung.90215.2008.-Fibroblasts are key structural cells that can be damaged by cigarette smoke. Cigarette smoke contains many components capable of eliciting oxidative stress, which may induce heme oxygenase (HO)-1, a cytoprotective enzyme. There are no data on HO-1 expression in primary human lung fibroblasts after cigarette smoke extract (CSE) exposure. We hypothesized that human lung fibroblasts exposed to cigarette smoke would increase HO-1 though changes in intracellular glutathione (GSH). Primary human lung fibroblasts were exposed to CSE, and changes in HO-1 expression and GSH levels were assessed. CSE induced a time-and dose-dependent increase in expression of HO-1, but not HO-2 or biliverdin reductase, in two different primary human lung fibroblast strains, a novel finding. This induction of HO-1 paralleled a decrease in intracellular GSH, and a sustained reduction in GSH resulted in a dramatic increase in HO-1. Treatment with the antioxidants N-acetyl-L-cysteine or GSH reduced the expression of HO-1 induced by CSE. We also examined the signal transduction mechanism responsible for HO-1 induction. Nuclear factor erythroid-derived 2, like 2 (Nrf2) was not involved in HO-1 induction by CSE. Activator protein-1 (AP-1) is a redox-sensitive transcription factor shown in other systems to regulate HO-1 expression. CSE exposure resulted in nuclear accumulation of c-Fos and c-Jun, two key AP-1 components. Reduction of c-Fos and c-Jun nuclear translocation by SP-600125 attenuated the CSE-induced expression of HO-1. These data support the concept that changes in the cellular redox status brought on by cigarette smoke induce HO-1 in fibroblasts. This increase in HO-1 may help protect against cigarette smoke-induced inflammation and/or cell death. oxidative stress; activator protein-1; biliverdin reductase; chronic obstructive pulmonary disease; nuclear factor erythroid-derived 2, like 2 HEME OXYGENASE (HO) enzymes catalyze the rate-limiting step in the oxidative degradation of heme to form equimolar amounts of ferrous iron, carbon monoxide (CO), and biliverdin (60, 69). Biliverdin is subsequently converted to bilirubin by biliverdin reductase (BVR). Two isozymes of HO have been well-characterized: an inducible form, HO-1, and the constitutive form, HO-2. Under basal condition, HO-1 occurs at low to undetectable levels in most tissues, but its expression is rapidly increased in response to a variety of environmental stimuli, particularly those that produce oxidative stress and generate reactive oxygen species (49, 60).Cigarette smoke contains many compounds capable of eliciting oxidative stress, yielding an estimated 10 17 oxidant molecules per puff (14). Oxidative stress caused by cigarette smoke leads to bronchial and alveolar inflammation and lung cell death...

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Section: Discussionmentioning

confidence: 99%

Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione

Baglole

Sime²,

Phipps³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…28 Briefly, an amount of 50 g of siRNA diluted in 1 ml of ringer lactate was delivered by rapid injection (10 seconds) in the tail vein 4 hours after the first hour of exposure to CS or room air. HO-1-specific siRNA nucleotide sequences were as follows 21,22 : sense, 5Ј-AAGCCACACAGCACUAUGUAAdTdT-3Ј; and antisense, 5Ј-UUACAUAGUGCUGUGUGGCUUdTdT-3Ј. Nonspecific siRNA was provided by Qiagen (Courtaboeuf, France): sense, 5Ј-UUCUCCGAACGUGUCACGUdTdT-3Ј and antisense: 5Ј-ACGUGACACGUUCGGAGAAdTdT-3Ј.…”

Section: Experimental Protocol In Micementioning

confidence: 99%

“…In a previous study we verified that this protocol of administration of HO-1 si-RNA specifically decreased HO-1 protein expression in different organs (joint, lungs, spleen, and liver) in mice. 22 Sacrifice and lung sampling were as described in the experimental protocol for rats. Each experimental group included six to eight animals.…”

Section: Experimental Protocol In Micementioning

confidence: 99%

“…To complete these experiments, we examined whether down-regulating HO-1 potentiated mucus hypersecretion induced by CS by use of an in vivo siRNA strategy. We performed these experiments in mice, 21,22 thus expanding on the data obtained in rats. Finally, we analyzed the clinical implications of animal data by examining, in a sample of 507 participants from the European Community Respiratory Health Survey, 23 whether the aforementioned HO-1 gene promoter polymorphism, leading to low levels of HO-1 protein expression, was associated with increased chronic sputum prevalence, a symptom of respiratory mucus hypersecretion.…”

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Heme Oxygenase-1 Prevents Airway Mucus Hypersecretion Induced by Cigarette Smoke in Rodents and Humans

Almolki

Guénégou

Gołda

et al. 2008

The American Journal of Pathology

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We investigated the role of heme oxygenase-1 (HO-1), a powerful anti-inflammatory and anti-oxidant enzyme, in modulating cigarette smoke (CS)-induced mucus secretion. In both rats and mice, 5-day CS exposure increased HO-1 expression and activity, mucus secretion, MUCIN 5AC (MUC5AC) gene and protein expression, and local inflammation, along with up-regulation of dual oxidase 1 gene expression and both the activity and phosphorylation of the epidermal growth factor receptor, which is involved in MUC5AC induction. Pharmacological induction of HO-1 prevented these actions and inhibition of HO-1 expression by a specific siRNA potentiated them. In French participants to the European Community Respiratory Health Survey II (n ‫؍‬ 210, 30 to 53 years of age, 50% males) exposed to CS, a significant increase in the percentage of participants with chronic sputum was observed in those harboring at least one allele with a long (GT) n in the HO-1 promoter gene (>33 repeats), which is associated with a low level of HO-1 protein expression, compared with those with a short number of (GT)n repeats (21.7% versus 8.6% , P ‫؍‬ 0.047). No such results were observed in those who had never smoked (n ‫؍‬ 297). We conclude that HO-1 has a significant protective effect against airway mucus hypersecretion in animals and humans exposed to CS.

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“…HO-1 is a stress-response enzyme whose expression is induced by a variety of stimuli including oxidative stress, hypoxia, and proinflammatory cytokines (Applegate et al, 1991;Otterbein and Choi, 2000). HO-1 has been shown to display potent antioxidant, anti-inflammatory, and antiviral functions (Lee et al, 2003;Kruger et al, 2006;Benallaoua et al, 2007;Protzer et al, 2007;Tsuchihashi et al, 2007). Induction of HO-1 by metal protoporphyrins or gene transfer can exert beneficial effects in a variety of conditions such as liver injury, diabetes, and cerebral malaria (Sass et al, 2004;Kruger et al, 2006;Benallaoua et al, 2007;Pamplona et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Heme Oxygenase-1 Alleviates Mouse Hepatic Failure through Suppression of Adaptive Immune Responses

Wu²,

Jin³

et al. 2011

J Pharmacol Exp Ther

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Heme oxygenase-1 (HO-1) has protective effects on liver damage induced by noxious stimuli. The mechanism of action of HO-1 is not well understood. In the present study, we investigate the effect of HO-1 in a model of fulminant hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS). The expression of HO-1 mRNA and protein in the liver was increased after repeated administration of the HO-1 inducer cobalt protoporphyrin IX. We found that HO-1 protected mice from acute liver damage induced by P. acnes/LPS and prolonged survival. On the contrary, administration of the HO-1 inhibitor zinc protoporphyrin IX increased liver damage induced by P. acnes/LPS. Subsequently, to investigate the underlying mechanisms of HO-1 in the acute liver injury model, we primed mice with P. acnes only. We found that the expression of HO-1 mRNA and protein in dendritic cells (DCs) was increased after the administration of cobalt protoporphyrin IX. HO-1 decreased the mature markers major histocompatibility complex II and CD80 on liver DCs. The expression of CCR7, CCL2, and CCL22 mRNA, which are expressed by mature DCs, was also reduced. These liver DCs could not efficiently stimulate CD4 ϩ T cell activation and proliferation. Consequently, HO-1 inhibited the activation, proliferation, and T helper 1 polarization of liverinfiltrating CD4ϩ T cells and reduced the production of serum alanine aminotransferase and proinflammatory cytokines such as interferon-␥ and tumor necrosis factor-␣. Taken together, our data suggest that HO-1 alleviates P. acnes/LPS-induced fulminant hepatic failure, probably by inhibiting DC-induced adaptive responses.

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Pharmacologic induction of heme oxygenase 1 reduces acute inflammatory arthritis in mice

Cited by 65 publications

References 40 publications

Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione

Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione

Heme Oxygenase-1 Prevents Airway Mucus Hypersecretion Induced by Cigarette Smoke in Rodents and Humans

Heme Oxygenase-1 Alleviates Mouse Hepatic Failure through Suppression of Adaptive Immune Responses

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