Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice

Lee, Tzong‐Shyuan; Chau, Lee‐Young

doi:10.1038/nm0302-240

Cited by 958 publications

(768 citation statements)

References 39 publications

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“…This Th2 cytokine exhibits a wide range of interactions with HO-1. For example, carbon monoxide has been shown to mediate the antiinflammatory effects of IL-10 in a mouse model of septic shock (35). In addition, exogenous administration of HO-1 increases IL-10 production in macrophages, which leads to the resolution of neutrophilic migration in the lung after lipopolysaccharide administration (36).…”

Section: Discussionmentioning

confidence: 99%

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Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Devesa¹,

Ferrándiz²,

Terencio³

et al. 2005

Arthritis & Rheumatism

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Objective. Heme oxygenase 1 (HO-1) can be induced by inflammatory mediators as an adaptive response. The objective of the present study was to determine the consequences of HO-1 modulation in the murine collagen-induced arthritis (CIA) model.Methods. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 22 to day 29 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, joints were examined for histopathologic changes. Cytokine levels in paws were measured by enzyme-linked immunosorbent assay. Levels of HO-1, cyclooxygenase 2 (COX-2), and prostaglandin E 2 (PGE 2 ) were determined. Effects of treatments on the early phase of disease and after prophylactic administration were also assessed.Results. CoPP strongly induced HO-1, resulting in the inhibition of cartilage erosion accompanied by extensive fibrosis in the joint. Levels of tumor necrosis factor ␣ (TNF␣), interleukin-2 (IL-2), and IL-10 were inhibited by CoPP, whereas levels of vascular endothelial growth factor were increased. Treatment with SnPP significantly reduced the severity of CIA, with inhibition of joint inflammation and cartilage destruction. The levels of PGE 2 , IL-1␤, and TNF␣ were also significantly reduced by SnPP treatment, which did not modify COX-2 protein expression. SnPP was more effective than CoPP in preventing the development of CIA (prophylactic administration).Conclusion. HO-1 is induced during CIA. Although overexpression of this protein causes some beneficial effects, strategies aimed at HO-1 overexpression cannot slow the progression of the chronic inflammatory disease, whereas treatment with SnPP, which inhibits HO-1, exerts prophylactic and therapeutic effects.

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Section: Discussionmentioning

confidence: 99%

“…For studies of prophylactic therapy, CoPP (2.5 mg/kg of body weight, intraperitoneally twice a day) or SnPP (6 mg/kg of body weight, intraperitoneally twice a day) was administered from day 20 (before clinical evidence of CIA) until day 34 after immunization (prophylactic group), and animals were killed by cervical dislocation on day 35.…”

Section: Methodsmentioning

confidence: 99%

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Devesa¹,

Ferrándiz²,

Terencio³

et al. 2005

Arthritis & Rheumatism

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“…Several mechanisms, either transcriptional or post-transcriptional, have been suggested to mediate this IL-10 effect. Very recently, Lee [18] argued that the anti-inflammatory effects of IL-10 are mainly mediated via HO-1 induction and an autocrine loop of its product CO. In contrast, we clearly show that although HO-1 is moderately up-regulated by IL-10 in vivo and in vitro in the human system, HO-1 is not responsible for mediating the anti-inflammatory effects of IL-10.…”

Section: Discussionmentioning

confidence: 99%

“…Lee et al [18] described for murine macrophages a strong up-regulation of HO-1 by IL-10, which was made responsible for the inhibition of LPS-induced TNF- § production. We could detect an IL-10-induced up-regulation of HO-1 expression in human peripheral monocytes by Affymetrix TM in vivo and in vitro.…”

Section: Role Of Ho-1 In Il-10 Effects On Monocytesmentioning

confidence: 99%

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Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

et al. 2004

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Interleukin‐10 (IL‐10), originally identified as an inhibitor of pro‐inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL‐10 functions. We aimed at identifying possiblemediators of in vitro IL‐10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with 12,000 genes. To prove relevance of the identified genes for the clinicalsituation we compared these in vitro results with genes being regulated by IL‐10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL‐10 therapy. A high proportion of the 1,600 genes up‐regulated and 1,300 genes down‐regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL‐10, can be assigned to known IL‐10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL‐10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up‐regulation of heme oxygenase‐1 (HO‐1). However, we demonstrate that the anti‐inflammatory mechanisms of IL‐10 remain functional even when HO‐1 is irreversibly inhibited.

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Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

Szabó

2010

Burger's Medicinal Chemistry and Drug Discovery

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Nitric oxide ( NO ), carbon monoxide ( CO ), and hydrogen sulfide ( H 2 S ) are the main endogenous gasotransmitters. These gases are produced by the body by enzymatic reactions and serve physiological regulatory purposes including vasodilatation and anti‐inflammatory effects. Over the past decades, multiple approaches have been identified for the therapeutic exploitation of these three gasotransmitters, based on inhalation of the gases and/or the parenteral or enteral administration of various formulations of these molecules or their prodrugs. Here we overview the medicinal chemistry and the therapeutic applications of NO, CO, and H 2 S and their prodrugs. Inhaled NO is used clinically to selectively dilate the pulmonary vasculature in the therapy of the primary pulmonary hypertension of the newborn. Organic nitrates such as glyceryl trinitrate or nitroglycerin are used in the therapy of acute and chronic angina. Sodium nitroprusside is used to counteract acute hypertensive crisis. Another class of clinical‐stage NO donor drugs is the sydnonimines (molsidomine, linsidomine). Additional classes of NO donors include diazeniumdiolates (NONOates) and S ‐nitrosothiols, with beneficial effects in various preclinical models of disease. With respect to CO, the main therapeutic approaches are CO inhalation (currently in clinical trials for the experimental therapy of delayed graft function associated with kidney transplantation) and carbon monoxide releasing compounds of various classes (in preclinical stage). With respect to H 2 S, a parenteral injectable formulation of the gas is currently is Phase I trials. Several classes of H 2 S donor molecules have also been identified, which are used in preclinical studies.

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Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice

Cited by 958 publications

References 39 publications

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

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Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice

Cited by 958 publications

References 39 publications

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH2Sand their Prodrugs

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Product

Resources

About

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs