Inhibition by fenoterol of human eosinophil functions includingβ2-adrenoceptor-independent actions

Tachibana, Akira; Katô, Masahiko; Kimura, Hirokazu; Fujiu, T; Suzuki, Masato; Morikawa, Akihiro

doi:10.1046/j.1365-2249.2002.01997.x

Cited by 23 publications

(24 citation statements)

References 60 publications

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“…The drugs that most completely activate a receptor are referred to as full agonists, while those that only partially activate the receptor are referred to as partial agonists. The main effects of β 2 -agonists are considered to be mediated by cAMP-dependent processes and the dependent kinase (protein kinase A; PKA) via adenylylcyclase to prevent inflammatory reactions [14, 16, 22]. …”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that several β 2 -agonists suppress allergen-induced recruitment of granulocytes in the lungs and airways [8, 9]. In addition, previous studies indicated inhibitory effects of long-acting β 2 -agonists and adrenergic agonists on granulocyte functions [10,11,12,13,14]. Furthermore, these agents have also been shown to have regulatory effects on the mechanism of bone marrow granulocyte hemopoiesis [15].…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Short-Acting β2-Agonists on Human Granulocyte Functions

Yasui¹,

Kobayashi²,

Yamazaki³

et al. 2005

Int Arch Allergy Immunol

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Background: β₂-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting β₂-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells. Methods: We examined whether widely used short-acting β₂-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O₂^–) production and degranulation. Results: Procaterol (PC), a full agonist, significantly inhibited both O₂^– production by granulocytes (neutrophils and eosinophils) and their degranulation at the clinically relevant concentrations, whereas salbutamol and tulobuterol (partial agonists) showed smaller effects. PC inhibited N-formyl methionyl-leucyl-phenylalanine-induced O₂^– production and peroxidase release, but failed to inhibit responses induced by phorbol 12-myristate 13-acetate and/or opsonized zymosan. Exposure to 5 × 10^–8M PC for 120 min resulted in approximately 50% inhibition of O₂^– production and degranulation of neutrophils. The effects of β₂-agonists were more obvious in neutrophils than in eosinophils. A selective β₂-receptor antagonist, ICI-118551, reversed the inhibitory effect of β₂-agonists (PC, salbutamol, tulobuterol B) on N-formyl methionyl-leucyl-phenylalanine-induced O₂^– production. Conclusions: These results suggest that β₂-agonists had an inhibitory effect on granulocyte functions, mainly mediated viareceptors and their efficacy. Our observations support that β₂-agonists with a rapid onset of action and high intrinsic efficacy (short-acting and full agonists) may be optimal for the rescue therapy against acute asthma attack and sedation of its airway inflammation in an early phase.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Effects of Short-Acting β2-Agonists on Human Granulocyte Functions

Yasui¹,

Kobayashi²,

Yamazaki³

et al. 2005

Int Arch Allergy Immunol

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“…Procaterol, the synthetic β 2 -adrenoceptor agonist widely used as a bronchodilator in asthma, has been reported to have anti-inflammatory effects on human eosinophils [13, 14]. In this study, we investigated the effect of procaterol on the expression of PPARγ in human eosinophil and its cell line EoL-1.…”

Section: Introductionmentioning

confidence: 99%

Procaterol Upregulates Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils

Ueki

Usami²,

Oyamada³

et al. 2006

Int Arch Allergy Immunol

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Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARγ and that stimulation with a synthetic agonist for PPARγ attenuated the factor-induced eosinophil activations. However, the modulator of PPARγ expression in eosinophils has not yet been studied. In this study, we investigated the effect of procaterol, the synthetic β₂-adrenoceptor agonist widely used as bronchodilators in asthma, on the PPARγ expression in eosinophils. Purified human peripheral blood eosinophil and the eosinophilic cell line EoL-1 were cultured with procaterol. This was followed by PPARγ measurement using flow cytometer and quantitative real-time RT-PCR. We observed that PPARγ was constitutively expressed by EoL-1 and the purified eosinophils and that the therapeutic concentration (10^–9M) of procaterol markedly enhanced PPARγ protein expression, which was reversed by the selective β₂-adrenoceptor antagonist ICI-118551. The PPARγ mRNA expression in EoL-1 and eosinophils was also induced by procaterol. These findings suggest that procaterol could modulate the eosinophil function by increasing the expression of PPARγ.

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“…The ADRB2 gene encodes a beta-2 adrenergic receptor mediating catecholamine-induced activation of adenylate cyclase via G proteins. ADRB2 is a known drug target to treat asthma [92,93] and a number of SNPs in this gene are associated with asthma [94,95] and hypertension [96,97].…”

Section: Prioritization Of Candidate Genesmentioning

confidence: 99%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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Background: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or~22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension -713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system.

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Inhibition by fenoterol of human eosinophil functions includingβ2-adrenoceptor-independent actions

Cited by 23 publications

References 60 publications

Differential Effects of Short-Acting β<sub>2</sub>-Agonists on Human Granulocyte Functions

Differential Effects of Short-Acting β<sub>2</sub>-Agonists on Human Granulocyte Functions

Procaterol Upregulates Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

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