A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model

Kimura, Yo; Koya, Toshiyuki; Kagamu, Hiroshi; Shima, Kenjiro; Sakamoto, Hirotaka; Kawakami, Hidenori; Hoshino, Yoshifumi; Furukawa, Toshiki; Sakagami, Takuro; Hasegawa, Takashi; Narita, Masami; Suzuki, Eiichi; Narita, Ichiei

doi:10.1016/j.ejphar.2013.09.051

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…ONO-1301SR, a sustained-release form of ONO-1301, exerts the same effects accompanied by the downregulation of fibrosis-related cytokines (α-SMA, ECM, and TGF-β) and upregulation of cardioprotective cytokines hepatic growth factor (HGF), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SCDF-1) in a mouse transverse aortic constriction model [ 82 ]. Similar to the effect on the heart, ONO-1301MS may relieve the inflammation and remodeling that occur in individuals with asthma by suppressing airway hyperresponsiveness, allergic inflammation, and the development of remodeling in a chronic house dust mite-induced asthma model [ 83 ]. ONO-1301 attenuates pancreatic fibrosis by inhibiting monocyte activity not only through the induction of HGF but also through direct effects of ONO-1301 itself on a rat model of dibutyltin dichloride-induced chronic pancreatitis [ 84 ].…”

Section: Prostaglandinsmentioning

confidence: 99%

The Roles of Various Prostaglandins in Fibrosis: A Review

Zhao

Wang

et al. 2021

Biomolecules

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Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular matrix and eventually leads to the destruction of the tissue structure and impaired organ function. Prostaglandins are produced by arachidonic acid through cyclooxygenases and various prostaglandin-specific synthases. Prostaglandins bind to homologous receptors on adjacent tissue cells in an autocrine or paracrine manner and participate in the regulation of a series of physiological or pathological processes, including fibrosis. This review summarizes the properties, synthesis, and degradation of various prostaglandins, as well as the roles of these prostaglandins and their receptors in fibrosis in multiple models to reveal the clinical significance of prostaglandins and their receptors in the treatment of fibrosis.

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Section: Prostaglandinsmentioning

confidence: 99%

The Roles of Various Prostaglandins in Fibrosis: A Review

Zhao

Wang

et al. 2021

Biomolecules

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“…PGI 2 is also a vasodilator that inhibits injury-induced vascular muscle proliferation and platelet activation and specifically inhibits the response to TxA 2 (16). A single injection of a sustained-release PGI 2 analog suppresses airway inflammation and remodeling in an asthma model (27). Similar inhibition of bronchial smooth muscle may result in the improved lung resistance noted in our model.…”

Section: Discussionmentioning

confidence: 59%

Iloprost attenuates hyperoxia-mediated impairment of lung development in newborn mice

Olave

Lal

Halloran

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Cyclooxygenase-2 (COX-2/PTGS2) mediates hyperoxia-induced impairment of lung development in newborn animals and is increased in the lungs of human infants with bronchopulmonary dysplasia (BPD). COX-2 catalyzes the production of cytoprotective prostaglandins, such as prostacyclin (PGI), as well as proinflammatory mediators, such as thromboxane A2. Our objective was to determine whether iloprost, a synthetic analog of PGI, would attenuate hyperoxia effects in the newborn mouse lung. To test this hypothesis, newborn C57BL/6 mice along with their dams were exposed to normoxia (21% O) or hyperoxia (85% O) from 4 to 14 days of age in combination with daily intraperitoneal injections of either iloprost 200 µg·kg·day, nimesulide (selective COX-2 antagonist) 100 mg·kg·day, or vehicle. Alveolar development was estimated by radial alveolar counts and mean linear intercepts. Lung function was determined on a flexiVent, and multiple cytokines and myeloperoxidase (MPO) were quantitated in lung homogenates. Lung vascular and microvascular morphometry was performed, and right ventricle/left ventricle ratios were determined. We determined that iloprost (but not nimesulide) administration attenuated hyperoxia-induced inhibition of alveolar development and microvascular density in newborn mice. Iloprost and nimesulide both attenuated hyperoxia-induced, increased lung resistance but did not improve lung compliance that was reduced by hyperoxia. Iloprost and nimesulide reduced hyperoxia-induced increases in MPO and some cytokines (IL-1β and TNF-α) but not others (IL-6 and KC/Gro). There were no changes in pulmonary arterial wall thickness or right ventricle/left ventricle ratios. We conclude that iloprost improves lung development and reduces lung inflammation in a newborn mouse model of BPD.

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“…(Zhou et al, 2014) Administration of the sustained-release PGI 2 analog ONO-1301M, that also had thromboxane A2 synthase inhibitory activity blocked airways responsiveness, Th2 cytokine production, airway eosinophils, airway smooth muscle hypertrophy, goblet cell metaplasia, and submucosal fibrosis in chronic house dust mite and ovalbumin models of allergic inflammation. (Kimura et al, 2013; Yamabayashi et al, 2012) PGI 2 not only restrains the adaptive allergic response, but PGI 2 signaling through IP additionally reduced innate immunity-mediated allergic inflammation. In a mouse model of 4 consecutive days of airway challenge with Alternaria alternata extract, endogenous PGI 2 signaling significantly reduced the number of lung IL-5 and IL-13-expressing ILC2 and mucous metaplasia, while inhaled cicaprost inhibited these same inflammatory endpoints.…”

Section: Individual Pgsmentioning

confidence: 99%

Prostaglandins in asthma and allergic diseases

Peebles

2019

Pharmacology & Therapeutics

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Prostaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD, PGE, PGF, PGI, and thromboxane B, that all signal through distinct seven transmembrane, G-protein coupled receptors. The receptors through which the prostaglandins signal determines their immunologic or physiologic effects. For instance, the same prostaglandin may have opposing properties, dependent upon the signaling pathways activated. In this article, we will detail how inhibition of cyclooxygenase metabolism and regulation of prostaglandin signaling regulates allergic airway inflammation and asthma physiology. Possible prostaglandin therapeutic targets for allergic lung inflammation and asthma will also be reviewed, as informed by human studies, basic science, and animal models.

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A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model

Cited by 8 publications

References 26 publications

The Roles of Various Prostaglandins in Fibrosis: A Review

The Roles of Various Prostaglandins in Fibrosis: A Review

Iloprost attenuates hyperoxia-mediated impairment of lung development in newborn mice

Prostaglandins in asthma and allergic diseases

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