Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5

Adachi, Tomohiko; Motojima, Seiji; Hirata, Akira; Fukuda, Takeshi; Kihara, Norio; Kosaku, Akinori; Ohtake, Hideki; Makino, Sohei

doi:10.1016/s0091-6749(96)70068-4

Cited by 93 publications

(53 citation statements)

References 36 publications

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“…Airway inflammation in asthma is characterized by an accumulation of activated eosinophils and lymphocytes in the airways [17,18]. Mice lacking EBI-3 had decreased degranulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

Hausding¹,

Karwot²,

Scholtes³

et al. 2007

Eur J Immunol

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Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3 -/-mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1 + cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c + cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c + cells isolated from EBI-3 -/-mice express markers of a more plasmacytoid phenotype without releasing IFN-a as compared to those from wildtype littermates. Moreover, allergen challenge induced the development of myeloid CD11c + cells in the lungs of EBI-3 -/-mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-a. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in the lungs in experimental asthma.

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“…Airway inflammation in asthma is characterized by an accumulation of activated eosinophils and lymphocytes in the airways [17,18]. Mice lacking EBI-3 had decreased degranulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

Hausding¹,

Karwot²,

Scholtes³

et al. 2007

Eur J Immunol

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“…Eosinophils are also notoriously difficult to study for a number of reasons: their paucity in the peripheral blood of normal, healthy volunteer blood donors, the laborious isolation techniques required to ensure a pure population and their relative intractability to standard molecular biological techniques such as siRNA. Corticosteroids are known to induce significant eosinophil apoptosis, in vitro, but it is still debatable as to whether this effect is relevant in vivo [6,31,[36][37][38][39][40]. Steroid drugs are extremely effective in the majority of asthmatic patients but some, at the more severe end of the spectrum, are resistant and others experience intolerable and unacceptable side-effects [41][42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%

The CDK inhibitor, R‐roscovitine, promotes eosinophil apoptosis by down‐regulation of Mcl‐1

Duffin¹,

Leitch²,

Sheldrake³

et al. 2009

FEBS Letters

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a b s t r a c tEosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.

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“…Importantly, macrolides, such as CAM and EM, have been reported to suppress the IL-5-induced prolongation of eosinophil survival. [4] Moreover, EM and its derivatives also inhibit proliferation and induce apoptosis of T-lymphocytes that secrete IL-5.…”

Section: Discussionmentioning

confidence: 99%

“…[2,3] Macrolides, such as clarithromycin (CAM) and erythromycin (EM), and calcineurin inhibitors, such as cyclosporine A (Cy-A) and tacrolimus (TAC), have been reported to exhibit immunomodulatory effects, including anti-T lymphocytic, and antieosinophilic effects that are thought to be related to IL-5. [4][5][6][7][8] We herein report a case of EGPA treated with glucocorticoids in combination with CAM and TAC considering their immunomodulatory effects.…”

Section: Introductionmentioning

confidence: 99%

Successful additional clarithromycin and tacrolimus treatment for hypereosinophilia associated with eosinophilic granulomatosis with polyangiitis

Ohe

Shida

Horita

et al. 2018

Transl Clin Pharmacol

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A 41-year-old man suffering from eosinophilic granulomatosis with polyangiitis (EPGA), diagnosed at another clinic on the basis of American College of Rheumatology Criteria, with a history of bronchial asthma, eosinophilia, mononeuritis multiplex, and non-fixed pulmonary infiltrates, was admitted to our department for further treatment. The patient complained of chest pain that started recently. An echocardiogram identified myocardial thickening and decreased wall motion, based on which the patient was diagnosed as having EPGA with myocarditis. The patient was successfully treated using glucocorticoids, such as methyl prednisolone (PSL) and PSL in combination with cyclophosphamide (CPM). However, CPM administration was discontinued afterwards because of the risk of bone marrow toxicity, the increased eosinophilic count (EOC) that we considered as an index of disease activity. Subsequently, the patient received additional clarithromycin (CAM) and tacrolimus (TAC) treatment considering their immunomodulatory effects. As a result, the EOC decreased and the PSL dosage could be reduced. This case shows that additional CAM and TAC treatment may be beneficial in some cases of EPGA.

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Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5

Cited by 93 publications

References 36 publications

Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

The CDK inhibitor, R‐roscovitine, promotes eosinophil apoptosis by down‐regulation of Mcl‐1

Successful additional clarithromycin and tacrolimus treatment for hypereosinophilia associated with eosinophilic granulomatosis with polyangiitis

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Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5

Cited by 93 publications

References 36 publications

Lung CD11c+ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

Lung CD11c+ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

The CDK inhibitor, R‐roscovitine, promotes eosinophil apoptosis by down‐regulation of Mcl‐1

Successful additional clarithromycin and tacrolimus treatment for hypereosinophilia associated with eosinophilic granulomatosis with polyangiitis

Contact Info

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Resources

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Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma

Lung CD11c⁺ cells from mice deficient in Epstein‐Barr virus‐induced gene 3 (EBI‐3) prevent airway hyper‐responsiveness in experimental asthma