A prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice

Hayashi, Masachika; Koya, Toshiyuki; Kawakami, Hidenori; Sakagami, Takuro; Hasegawa, Takashi; Kagamu, Hiroshi; Takada, Tsuneo; Sakai, Yoshiki; Suzuki, Eiichi; Gelfand, Erwin W.; Gejyo, Fumitake

doi:10.1111/j.1365-2222.2009.03418.x

Cited by 16 publications

(12 citation statements)

References 23 publications

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“…AHR was assessed by measuring changes in respiratory resistance in response to increasing doses of inhaled methacholine (MCh) using the Flexivent system (SCIREQ, Montreal, Que., Canada), as previously reported [19] .…”

Section: Airway Responsivenessmentioning

confidence: 72%

The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma

Sakamoto

Koya²,

Tsukioka³

et al. 2015

Int Arch Allergy Immunol

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Background: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4⁺ T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. Results: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4⁺ T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. Conclusion: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion.

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Section: Airway Responsivenessmentioning

confidence: 72%

The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma

Sakamoto

Koya²,

Tsukioka³

et al. 2015

Int Arch Allergy Immunol

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“…ONO-1301 also has thromboxane-synthase inhibitory activity because of the presence of a 3-pyridine radical. We previously demonstrated that ONO-1301 prevents acute airway inflammation in murine models of allergic asthma through the inhibition of lung dendritic cell functions (10). In the present study, we investigated whether this compound exerted an effect on the alteration of AHR and airway remodeling in a model of chronic asthma.…”

mentioning

confidence: 84%

A Novel Prostacyclin Agonist Protects against Airway Hyperresponsiveness and Remodeling in Mice

Yamabayashi

Koya

Kagamu

et al. 2012

Am J Respir Cell Mol Biol

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Airway remodeling in bronchial asthma results from chronic, persistent airway inflammation. The effects of the reversal of airway remodeling by drug interventions remain to be elucidated. We investigated the effects of ONO-1301, a novel prostacyclin agonist with thromboxane inhibitory activity, on the prevention and reversibility of airway remodeling in an experimental chronic asthma model. Mice sensitized and challenged to ovalbumin (OVA) three times a week for 5 consecutive weeks were administered ONO-1301 or vehicle twice a day from the fourth week of OVA challenges. Twenty-four hours after the final OVA challenge, airway hyperresponsiveness (AHR) was assessed, and bronchoalveolar lavage was performed. Lung specimens were excised for staining to detect goblet-cell metaplasia, airway smooth muscle, and submucosal fibrosis. Mice administered ONO-1301 showed limited increases in AHR compared with mice administered the vehicle. The histological findings of airway remodeling were improved in ONO-1301-treated mice compared with vehicle-treated mice. Presumably, these therapeutic effects of ONO-1301 are attributable to the up-regulation of production of hepatocyte growth factor (HGF) in lung tissue, because the neutralization of HGF by antibodies prevented the effects of ONO-1301 on AHR and airway remodeling. Mice administered ONO-1301 showed similar levels of AHR and airway remodeling as mice administered montelukast, a cysteinyl-leukotriene-1 receptor antagonist, and lower levels were observed in mice administered dexamethasone. These data suggest that ONO-1301 exerts the effect of reversing airway remodeling, at least in part through an elevation of HGF in the lungs, and may be effective as an anti-remodeling drug in the treatment of asthma.

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“…Hayashi et al [88] reported in 2010 that administration of ONO-1301 was more therapeutic for ovalbumin-induced asthma model in mice than beraprost. In addition, Kimura et al [89] tested the hypothesis that ONO-1301SR treatment is effective in suppressing hyperresponsiveness, allergic inflammation and remodelling of the airway.…”

Section: Ono-1301/ono-1301sr Treatment For Extracardiac Pathologiesmentioning

confidence: 99%

A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

et al. 2015

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Cardiac failure is a major cause of mortality and morbidity worldwide, since the standard treatment for cardiac failure in the clinical practice is chiefly to focus on removal of insults against the heart or minimisation of additional factors to exacerbate cardiac failure, but not on regeneration of the damaged cardiac tissue. A synthetic prostacyclin agonist, ONO-1301, has been developed as a long-acting drug for acute and chronic pathologies related to regional ischaemia, inflammation and/or interstitial fibrosis by pre-clinical studies. In addition, poly-lactic co-glycolic acid-polymerised form of ONO-1301, ONO-1301SR, was generated to achieve a further sustained release of this drug into the targeted region. This unique reagent has been shown to act on fibroblasts, vascular smooth muscle cells and endothelial cells in the tissue via the prostaglandin IP receptor to exert paracrinal release of multiple protective factors, such as hepatocyte growth factor, vascular endothelial growth factor or stromal cell-derived factor-1, into the adjacent damaged tissue, which is salvaged and/or regenerated as a result. Our laboratory developed a new surgical approach to treat acute and chronic cardiac failure using a variety of animal models, in which ONO-1301SR is directly placed over the cardiac surface to maximise the therapeutic effects and minimise the systemic complications. This review summarises basic and pre-clinical information of ONO-1301 and ONO-1301SR as a new reagent to enhance tissue salvage and/or regeneration, with a particular focus on the therapeutic effects on acute and chronic cardiac failure and underlying mechanisms, to explore a potential in launching the clinical study.

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A prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice

Abstract: These data suggest that ONO-1301 may suppress AHR and airway allergic inflammation through modulation of DCs, mainly mediated through the IP receptor. This agent may be effective as an anti-inflammatory drug in the treatment of asthma.

Cited by 16 publications

References 23 publications

The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma

The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma

A Novel Prostacyclin Agonist Protects against Airway Hyperresponsiveness and Remodeling in Mice

A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

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