• IMMUNE NETWORK
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• v.19 no.1
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• pp.5.1-5.12
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• 2019

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

• BMB Reports
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• v.54 no.3
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• pp.182-187
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• 2021

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDM-induced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDM-induced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.695-705
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• 2021

Background: Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods: We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results: We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion: Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.210.2-211
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• 2003

Eosinophilic inflammation is the main histological correlate of airway hyperresponsiveness and tissue injury in the pathogenesis of bronchial asthma. Interleukin (IL)-5 appears to be one of main proinflammatory mediators that induce eosinophilic inflammation. Allergic IL -5-deficient mice do not generate eosinophilia in the bone marrow, blood or lung in response to allergen provocation. (omitted)

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.49-57
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• 2011

Objective : Allergic asthma is a chronic airway disease that affects millions of people in the developed world. The disease is characterized by concurring airway inflammation, Th2 cytokine production, increased mucus secretion, airway hyperresponsiveness (AHR) to inhaled antigen, and pulmonary fibrosis. To investigate the therapeutic and anti-asthmatic effects of Drynariae Rhizoma (DR), we examined the influence of DR on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods : In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of DR on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA specific IgE production in a mouse model of asthma. Results : In asthmatic mice, we found that DR.treated groups had suppressed eosinophil infiltration, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13 and OVA specific IgE. Conclusions : Our data suggest that the therapeutic mechanism by which DR effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production and eosinophil infiltration.

• Journal of Veterinary Clinics
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• v.34 no.6
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• pp.481-483
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• 2017

A 2-year-old neutered male Bengal cat presented with a 6-month history of weight loss and chronic vomiting. An abdominal ultrasound revealed increased thickness of the pylorus and ascending duodenum with concurrent enlargement of the mesenteric lymph nodes. Histologically, branching and anastomosing trabecular pattern of dense collagen was the characteristic feature, and large populations of spindle cells were also observed. These large spindle-shaped cells were positive for smooth muscle actin and vimentin on immunohistochemical examination. Based on these findings, the cat was diagnosed with feline gastrointestinal eosinophilic slcerosing fibroplasia (FGESF), and immunosuppressive therapy was initiated immediately. Unfortunately, the cat's condition deteriorated despite treatment; the cat died 56 days after initiation of therapy. This is the first report of FGESF in South Korea.

• Molecules and Cells
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• v.42 no.4
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• pp.345-355
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• 2019

Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. FZD5 is a receptor for Wnt5A, and its complex with Wnt5A contributes to activating inflammation and tissue modification. Nasal polyps and eosinophil/non-eosinophil counts are reported to be directly correlated. This study investigated the expression and distribution of FZD5, and the role of eosinophil infiltration and FZD5 in eosinophilic CRSwNP pathogenesis. The prognostic role of eosinophil levels was evaluated in seven patients with CRSwNP. Fifteen patients with CRS were classified based on the percentage of eosinophils in nasal polyp tissue. Methylated genes were detected using methylCpG-binding domain sequencing, and qRT-PCR and immunohistochemistry were used to detect FZD5 expression in nasal polyp tissue samples. The results showed that mRNA expression of FZD5 was upregulated in nasal polyps. FZD5 expression was significantly higher in nasal polyp samples from patients with eosinophilic CRSwNP than in those from patients with non-eosinophilic CRSwNP, as indicated by immunohistochemistry. Furthermore, inflammatory cytokine levels were higher in eosinophilic CRSwNP-derived epithelial cells than in normal tissues. In conclusion, FZD5 expression in nasal mucosal epithelial cells is correlated with inflammatory cells and might play a role in the pathogenesis of eosinophilic CRSwNP.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.167-170
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• 2015

Hypereosinophilic syndrome (HES) is characterized by the presense of hypereosinophilia with evidence of target organ damage. We report a patient diagnosed with eosinophilic cystitis and HES. A 7 year old boy had hematuria, dysuria, and increased urinary frequency for 1 day. Laboratory examinations revealed hypereosinophilia (eosinophils, $2,058/{\mu}L$), hematuria, and proteinuria. Abdominal sonography revealed diffuse and severe wall thickening of the bladder. The patient was treated initially with antibiotics. However, his symptoms did not improve after 7 days. A computed tomography scan demonstrated severe wall thickening of the bladder and the hypereosinophilia persisted (eosinophils, $2,985/{\mu}L$). The patient complained of chest discomfort, dyspnea, epigastric pain, and vomiting on hospital day 10. Parasitic, allergic, malignancy, rheumatologic, and immune workups revealed no abnormal findings. Chest X-rays, electrocardiography, and a pulmonary function test were normal; however, the hypereosinophilia was aggravated (eosinophils, $3,934/{\mu}L$). Oral deflazacort was administered. A cystoscopic biopsy showed chronic inflammation with eosinophilic infiltration. The patient's respiratory, gastrointestinal, and urinary symptoms improved after 6 days of steroids, and he was discharged. The eosinophil count decreased dramatically ($182/{\mu}L$). The hypereosinophilia waxed and waned for 7 months, and the oral steroids were tapered and stopped. This case describes a patient diagnosed with eosinophilic cystitis and HES.

• Journal of Veterinary Clinics
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• v.39 no.2
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• pp.75-80
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• 2022

An 11-year-old male Rex rabbit (Oryctolagus cuniculus) had a rectal prolapse induced by a polypoid mass. The mass was highly vascularized with a cauliflower-like appearance. Anorectal papilloma was suspected, and fine needle aspiration cytology showed eosinophilic inflammation. After surgical removal of the polyp, postoperative care was given, such as systemic antibiotics and analgesics. In the re-examination, the rabbit was resolved, and there were no complications. Histopathological examination of the removed polyp indicated chronic eosinophilic proctitis to be the cause of the inflammatory condition of the protruding rectal polyp.

• Journal of Veterinary Clinics
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• v.39 no.4
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• pp.192-196
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• 2022

A two-year-old, intact male, 45 kg Doberman Pinscher was referred with dermal nodular lesions affecting the left hindlimb. The cytological examination revealed eosinophilic inflammation. Skin biopsy specimens showed canine eosinophilic granuloma (CEG). The dog was administered oral prednisolone (1.5 mg/kg/day) and azathioprine (2 mg/kg/day). After one week, the skin lesions diminished dramatically, but the dog presented with severe watery diarrhea. The prednisolone dose was reduced by 0.9 mg/kg/day. The lesions and diarrhea improved markedly after one week. Prednisolone was tapered by 25% of the previous dose every week to 0.2 mg/kg/day. Azathioprine was also reduced to therapy every other day. After seven weeks of combination treatment, the medications were withdrawn, but the dog had a recurrence one week later. Azathioprine (2 mg/kg/EOD) was reintroduced for two weeks. There was no relapse after all the medications had been withdrawn. This case indicates that CEG can be managed with prednisolone and azathioprine. Azathioprine may be an effective adjunctive immunosuppressive agent, and may be considered as a well-tolerated prednisolone sparing agent to treat CEG.