Heme oxygenase‐1 (HO‐1) protein induction in a mouse model of asthma

Kitada, O; Kodama, Taku; Kuribayashi, Kozo; Ihaku, Daizo; Fujita, Mitsugu; Matsuyama, Takashi; Sugita, Minoru

doi:10.1046/j.1365-2222.2001.01179.x

Cited by 43 publications

(37 citation statements)

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“…Recent studies demonstrate increased expression of the 32-kDa stress protein HO-1, the principal biological source of CO, in preclinical models of asthma and in human asthma (7,18,21). HO-1 responds to induction by a variety of agents, including ultraviolet A radiation, thiol-reactive substances, nitric oxide, and proinflammatory cytokines (6,17).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

Song

Ning

Liu

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Asthma, a chronic inflammatory disease of the airways, involves the increased expression of inflammatory mediators, including granulocyte-monocyte colony-stimulating factor (GM-CSF). Heme oxygenase-1 (HO-1), a stress-response protein, confers protection against oxidative stress. We hypothesized that carbon monoxide (CO), a byproduct of HO-1-dependent heme catabolism, regulates GM-CSF synthesis in human airway smooth muscle cells (HASMC). IL-1β treatment induced a time-dependent induction of GM-CSF in HASMC. Furthermore, IL-1β stimulated the major MAPK pathways, including ERK1/ERK2, JNK, and p38 MAPK. Exposure of HASMC to CO at low concentration (250 ppm) markedly inhibited IL-1β-induced GM-CSF synthesis (>90%) compared with air-treated controls. CO treatment inhibited IL-1β-induced ERK1/2 activation but did not inhibit JNK and p38 MAPK. Furthermore, CO increased cGMP levels in HASMC. Inhibition of guanylate cyclase by IH-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1–1 (ODQ) abolished the inhibitory effects of CO on GM-CSF synthesis and ERK1/2 activation. Collectively, these data demonstrate that the inhibitory effect of CO on GM-CSF synthesis depends on ERK1/2 MAPK and guanylate cyclase/cGMP-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies showed elevated HO-1 expression in association with preclinical models of asthma and human asthma (7,18,21). Several laboratories also detected elevated levels of CO in the breath of patients with asthma (14).…”

mentioning

confidence: 99%

Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

Song

Ning

Liu

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Previous study suggested HO-1 could protect against airway inflammation by down-regulating tumor necrosis factor receptor (TNFR)1 dependent oxidative stress [30] . In asthma particularly, it was considered that the increase of HO-1 expression and activity were protective [31] . The anti-asthmatic effects of Ulmus davidiana var japonica were also found associated with up-regulating airway HO-1 [32,33] .…”

Section: Discussionmentioning

confidence: 99%

The PPARγ agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma

Zhu

Wang

et al. 2015

Acta Pharmacol Sin

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Aim: Rosiglitazone is one of the specific PPARγ agonists showing potential therapeutic effects in asthma. Though PPARγ activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 (HO-1) related pathways were involved in rosiglitazone-activated PPARγ signaling in asthma treatment. Methods: Asthma was induced in mice by multiple exposures to ovalbumin (OVA) in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone (5 mg/kg, po). After the mice were sacrificed, the bronchoalveolar lavage fluid (BALF), blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARγ, HO-1 and p21 proteins was also examined. Results: Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARγ, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP. Conclusion: Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA-induced asthma of mice by activating PPARγ/HO-1 signaling pathway.

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“…In addition, exhaled CO levels are elevated in individuals with asthma (43), and while some studies have shown an increase upon allergen challenge (45) and a decrease with corticosteroids (46), other studies have shown no effect (44). In a murine model of asthma, HO-1 expression is increased in the airway lumen and bronchial submucosa of antigen-challenged mice (47). In addition, Almolki and colleagues recently demonstrated that up-regulation of HO-1 by hemin decreased airway inflammation, mucus secretion, and airway responsiveness to histamine in ovalbumin-sensitized guinea pigs (48).…”

Section: Asthmamentioning

confidence: 99%

The Role of Heme Oxygenase-1 in Pulmonary Disease

Fredenburgh

Perrella

Mitsialis

2007

Am J Respir Cell Mol Biol

181

165

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Heme oxygenase (HO)-1, the inducible isoform of heme oxygenase, is a cytoprotective enzyme that plays a central role in the defense against oxidative and inflammatory insults in the lung. HO-1 catalyzes the degradation of heme, a potent oxidant, into biliverdin, iron, and carbon monoxide (CO). These downstream products of heme catabolism have recently been found to mediate the antioxidant, antiapoptotic, antiproliferative, vasodilatory, and anti-inflammatory properties of HO-1. Although absence of HO-1 is rare in humans, a number of HO-1 promoter polymorphisms have been identified that may influence HO-1 expression in vivo and lead to disease states. This review will summarize studies that implicate HO-1 and heme metabolites in the pathophysiology of pulmonary disease and discuss recent advances in the therapeutic applications of HO-1.Keywords: HO-1; polymorphism; ARDS; pulmonary hypertension; COPD THE ROLE OF HEME OXYGENASE-1 IN PULMONARY DISEASEHeme oxygenase (HO)-1, the inducible isoform of heme oxygenase, plays a critical role in defending the lung against inflammatory and oxidant-induced cellular and tissue injury. This cytoprotective enzyme catalyzes the degradation of heme, a potent oxidant, to generate biliverdin-IX␣, iron, and carbon monoxide (CO) (Figure 1) (1). Biliverdin-IX␣ is converted to bilirubin-IX␣, a potent endogenous antioxidant (2), with recently recognized anti-inflammatory properties (3), while iron is sequestered by ferritin, leading to additional antioxidant (4) and antiapoptotic (5) effects. CO has numerous biological functions, including anti-inflammatory properties (6, 7), and shares many similarities with nitric oxide (NO), such as its ability to inhibit smooth muscle cell proliferation (8, 9) and platelet aggregation (10), as well as modulate vascular tone by increasing cGMP levels (11).In the lung, HO-1 is expressed in various cells types, including type II pneumocytes and alveolar macrophages, and is induced by heme (12), hypoxia (13,14), hyperoxia (15), and NO (16), as well as endotoxin and proinflammatory cytokines (e.g., IL-6, (Received in final form September 3, 2006 ) This work was funded by T32 HL007633-21 (L.E.F.), RO1 HL60788 (M.A.P.), and R01 HL55454 (S.A.M.) from the National Institutes of Health.

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Heme oxygenase‐1 (HO‐1) protein induction in a mouse model of asthma

Abstract: The expression of HO-1 is increased within the lung tissue in allergic airway inflammation. Measurement of HO-1 activity may be clinically useful in the management of asthma.

Cited by 43 publications

References 38 publications

Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

The PPARγ agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma

The Role of Heme Oxygenase-1 in Pulmonary Disease

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