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Heme oxygenase-1: its therapeutic roles in inflammatory diseases.

Pae HO, Chung HT - Immune Netw (2009)

Bottom Line: HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation.The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1.This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Korea.

ABSTRACT
Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

No MeSH data available.


Related in: MedlinePlus

Induction of HO-1 and subsequent production of heme degradation products exert potent anti-oxidative, anti-inflammatory and anti-apoptotic functions for the tissue homeostasis. HO-1 can be expressed by a number of stimuli mainly via MAPK-dependent Nrf2 activation. These inducers of HO-1 include free heme, inflammatory mediators, oxidative stress, IL-10, and some inflammatory drugs. HO-1, once expressed under pathological conditions, can degrade free heme into BV, CO, and Fe2+. BV is converted into BR by BV reductase. The iron is rapidly sequestered by ferritin. Heme degradation products have been shown to modulate inflammatory response, perhaps by reducing oxidative stress, blocking MAPK pathways, and suppressing NF-κB activity.
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Figure 1: Induction of HO-1 and subsequent production of heme degradation products exert potent anti-oxidative, anti-inflammatory and anti-apoptotic functions for the tissue homeostasis. HO-1 can be expressed by a number of stimuli mainly via MAPK-dependent Nrf2 activation. These inducers of HO-1 include free heme, inflammatory mediators, oxidative stress, IL-10, and some inflammatory drugs. HO-1, once expressed under pathological conditions, can degrade free heme into BV, CO, and Fe2+. BV is converted into BR by BV reductase. The iron is rapidly sequestered by ferritin. Heme degradation products have been shown to modulate inflammatory response, perhaps by reducing oxidative stress, blocking MAPK pathways, and suppressing NF-κB activity.

Mentions: HO-1 expression is up-regulated in response to various forms of inflammatory stimuli, and this is associated with reduced inflammation (14). However, the mechanism(s) of anti-inflammatory actions of HO-1 has not been completely elucidated. It is most likely that the anti-inflammatory effects afforded by HO-1 may be attributed not only to its own action but also to other actions of three by-products of HO-1 activity (6). On other words, the degradation of the pro-oxidant heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of free iron by ferritin could all concertedly contribute to the anti-inflammatory effects observed with HO-1 (Fig. 1). The followings briefly describe the mechanisms that may explain the anti-inflammatory actions of HO-1.


Heme oxygenase-1: its therapeutic roles in inflammatory diseases.

Pae HO, Chung HT - Immune Netw (2009)

Induction of HO-1 and subsequent production of heme degradation products exert potent anti-oxidative, anti-inflammatory and anti-apoptotic functions for the tissue homeostasis. HO-1 can be expressed by a number of stimuli mainly via MAPK-dependent Nrf2 activation. These inducers of HO-1 include free heme, inflammatory mediators, oxidative stress, IL-10, and some inflammatory drugs. HO-1, once expressed under pathological conditions, can degrade free heme into BV, CO, and Fe2+. BV is converted into BR by BV reductase. The iron is rapidly sequestered by ferritin. Heme degradation products have been shown to modulate inflammatory response, perhaps by reducing oxidative stress, blocking MAPK pathways, and suppressing NF-κB activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803295&req=5

Figure 1: Induction of HO-1 and subsequent production of heme degradation products exert potent anti-oxidative, anti-inflammatory and anti-apoptotic functions for the tissue homeostasis. HO-1 can be expressed by a number of stimuli mainly via MAPK-dependent Nrf2 activation. These inducers of HO-1 include free heme, inflammatory mediators, oxidative stress, IL-10, and some inflammatory drugs. HO-1, once expressed under pathological conditions, can degrade free heme into BV, CO, and Fe2+. BV is converted into BR by BV reductase. The iron is rapidly sequestered by ferritin. Heme degradation products have been shown to modulate inflammatory response, perhaps by reducing oxidative stress, blocking MAPK pathways, and suppressing NF-κB activity.
Mentions: HO-1 expression is up-regulated in response to various forms of inflammatory stimuli, and this is associated with reduced inflammation (14). However, the mechanism(s) of anti-inflammatory actions of HO-1 has not been completely elucidated. It is most likely that the anti-inflammatory effects afforded by HO-1 may be attributed not only to its own action but also to other actions of three by-products of HO-1 activity (6). On other words, the degradation of the pro-oxidant heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of free iron by ferritin could all concertedly contribute to the anti-inflammatory effects observed with HO-1 (Fig. 1). The followings briefly describe the mechanisms that may explain the anti-inflammatory actions of HO-1.

Bottom Line: HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation.The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1.This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Korea.

ABSTRACT
Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

No MeSH data available.


Related in: MedlinePlus