• Parasites, Hosts and Diseases
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• 제38권1호
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• pp.17-23
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• 2000

Eosinophils are important effector cells in host defense against parasites. Excretory-secretory product (ESP) produced by helminthic worms plays important roles in the uptake of nutrients, migration in the host tissue, and in immune modulation. However little is known about the ability of the ESP to directly trigger eosinophil apoptosis. This study investigated whether the ESP of newly excysted metacercariae of Paragonimus westermani could induce apoptosis in human eosinophils. Apoptosis was assayed by staining the cells with FITC-annexin V, and the cells were analyzed by flow cytometry. It was found that the ESP of newly excysted metacercariae of P. westemani induced a direct time- and concentration-dependent increase in the rate of constitutive apoptosis in mature human eosinophils. Eosinophil apoptosis was first apparent 3 hr after treatment with the ESP and continued to increase after 6 hr of incubation with respect to the cells cultured in the absence of the ESP. While only 2.8% of the eosinophils incubated in the medium for 3 hr were apoptotic, 7.6%, 10.9% and 22.6% of the eosinophils treated with 10. 30 and $100{\;}\mu\textrm{g}/ml$ ESP were apoptotic, respectively. This result suggests that the ESP of newly excysted metacercariae of P. westermani directly induce eosinophil apoptosis, which may be important for the survival of the parasites and the reduction of eosinophilic inflammation in vivo.

• 대한의생명과학회지
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• 제20권1호
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• pp.39-42
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• 2014

Asthma is an allergic inflammation and house dust mite (HDM) is a major allergen to induce asthma pathogenesis. Regulation of eosinophil apoptosis is an essential immune process and its dysregulation is implicated in asthma. In the present study, we examined the effects of HDM on spontaneous apoptosis of asthmatic eosinophils and on cytokine secretion in eosinophils of normal subjects including non-atopic and atopic normal. Extract of Dermatophagoides pteronissinus (DP) inhibited eosinophil apoptosis in a time-dependent manner. DP increased the secretion of G-CSF, GM-SCF, and IL-4, which is involved in suppression of eosinophil apoptosis, but IL-5 expression was not altered after DP stimulation. DP also elevated the release of IL-6, IL-8, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and CCL2, which are anti-apoptotic or survival factors. The secretion of G-CSF, GM-CSF, IL-6, IL-8, and TNF-${\alpha}$ due to DP is higher in atopic normal than that in non-atopic normal. In conclusion, DP increases the survival of eosinophils and its mechanism may be associated with cytokine release. These findings may enable elucidation of asthma pathogenesis induced by HDM.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.451-459
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• 2024

Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.

• 사상체질의학회지
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• 제16권2호
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• pp.84-98
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• 2004

1. Objectives Yangkyuksanhwa-tang is used mush in pruritus and dermatopathy of Soyangin. It is suggested this prescription is effective on atopy dermatitis. 2. Methods For observation of Yangkyuksanhwa-tang effected to atopic dermatitis, extract of Yangkyuksanhwa-tang has been dispensed to the stratum corneum of epithelium in dermatome of murine after making damage to its defense mechanism against fat and causing atopic dermatitis artificially. After that, the change in outer dermatome and minute mechanism of epidermis, the change of eosinophil, the change in distribution of soybean agglutinin, the change in distribution of fat and ceramide in stratum corneum, the change in inflammation in dermatome, the change of cell accrementition and apoptosis, and the effect on anaphylaxis and Staphylococcus aureus was observed. 3. Results After administration of Yangkyuksanhwa-tang, severe skin damage such as eczema and psoriasis, that was observed in the case of atopy dermatitis, was decreased and the increase of eosinophil in serum was suppressed. Lipid lamella was recovered, so epidermal demage was relieved. The distribution of HSP70 in the outer skin was decreased. Yangkyuksanhwa-tang suppressed activation of $NF-_{\kappa}B$ p50, induced CD11/18b not to be generated, and suppressed inflammatory response of skin. Anaphylaxis and groth of Staphylococcus aureus was suppressed. 4. Conclusions Yangkyuksanhwa-tang decreased skin damage of atopy dermatitis. It has antibiosis about Staphylococcus aureus, it can be medicinal substances on atopy dermatitis. In addition, it is possible that it can be medicinal substances on regional skin allergy.

• 대한의생명과학회지
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• 제23권1호
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• pp.44-47
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• 2017

S100A8 and S100A9 are associated with myeloid cell differentiation, chemotactic activities, adhesion of neutrophils, and apoptosis. In this study, we investigated the contribution of S100A8 and S100A9 to differentiation of the human eosinophilic leukemia cell line, EoL-1. S100A8 and S100A9 increased the number of vacuole per one cell and the protein expression of EPO and MBP. Rottlerin, an inhibitor of protein kinase C delta ($PKC{\delta}$), inhibited the EoL-1 cell differentiation induced by S100A8 and S100A9. These results suggest that S100A8 and S100A9 may regulate the differentiation of eosinophilic progenitors. Moreover, these findings may shed light on elucidation of eosinophil differentiation due to S100 proteins.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.254-254
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• 1996

Eosinophils are known to be important effector cells in pathogenesis of asthma. The elucidation of mechanism by which eosinophil survival is regulated in vivo at sites of inflammation is critical tn our understanding of asthma pathogenesis. The maintenance of these cells at site of inflammation depends upon tile balance between its tendency to undergo apoptosis and tile local eosinophil-viability enhancing activity, Qualitative and quantative phenotypic differences have been observed between bronchoalveolar lavage (BAL) and peripheral blood (PB) eosinophils (EOS). We hypothesize that BAL EOS Possess altered functional feature compared to PB EOS. BAL and PB EOS were obtained from ragweed allergic asthmatics after segmental antigen challenge (SAC) at 24 hour or one week, and purified over percoll and CDl6 negative selection. Cells were cultured in duplicate in RPMI, 15% FCS and 1% penicillin/streptomycin without exogenous cytokines. Eosinophil purity and viability was >92%. BAL. EOS viability was 69${\pm}$4.4% versus 39${\pm}$1.6% for PB EOS (p<0.005) at 48 hour time point, and this difference was maintained through day 5 (32${\pm}$7.6% vs. 3.0${\pm}$ 1.4%, p<0.05), Among BAL EOS, those harvested one week after SAC appeared to have an prolonged survival compared to those harvested at 24 hour. Coculture of BAL and PB EOS resulted in significant viability enhancement than expecteed. Direct neutralization of GM-CSF activity, not IL-3 and EL-5, markedly decreased tile survival of BAL EOS in culture, and abrogated tile viability enhancing activity of their culture supernatants in a dose dependent manner. We conclude that BAL EOS activated in vivo possess enhanced viability compared to PB EOS. Mixing and neutralization experiments suggest a role for autocrine production of GM-CSF.

• Tuberculosis and Respiratory Diseases
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• 제46권1호
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• pp.44-52
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• 1999

연구배경: 기관지천식은 호산구성 기도내 염증반응을 특징으로 하는데 호산구의 침윤에 관여하는 cytokine으로 T 림프구에서 분비되는 IL-3, IL-5, GM-CSF 등이 잘 알려져 있다. 한편 IL-10은 항염증성 cytokine으로 이러한 cytokine 분비를 억제할뿐만아니라, 호산구에 대해서는 직접적으로 자사(apoptosis)를 유도하고 조직내 첨착을 억제하는 기능을 갖고 있다. 본 연구에서는 기관지천식 환자에서의 기관지폐포세척액과 말초 혈액단핵세포에서 분비되는 IL-10을 정상대조군과 비교하고 기도내 염증반응정도와의 연관성을 분석하여 기관지천식에서의 IL-10 역할을 알아보고자 하였다. 방 법: 기관지천식환자 23명, 정상대조군 11명을 대상으로 기관지폐포세척액내와 말초혈액단핵구에서 분비되는 IL-10을 ELISA 방법으로 측정하고, 기도의 염증반응정도는 기관지세포세척액내 총세포수 및 호산구분율과 기관지 생검조직내 호산구 침윤정도, methacholine 기관지유발 검사에서 $PC_{20}$값으로 평가하였다. 결 과: 기관지폐포세척액내 IL-10과 말초혈액단핵구에서 분비되는 IL-10은 기관지천식 환자군과 정상대조군 사이에 통계적으로 유의한 차이는 없었다. 기관지천식환자군에서 기관지폐포세척액내 IL-10은 기관지폐포세척액내 호산구분율 및 기관지 조직내 침윤된 호산구수와는 유의한 역상관관계를 보였고, 메타콜린에 대한 PC20에 따른 차이는 없었다. 말초혈액단핵구에서 분비되는 IL-10은 기관지폐포세척액내 IL-10과 상관 관계가 없었으며, 말초혈액내 호산구수나 eosinophilic cationic protein과도 유의한 상관관계가 없었다. 결 론: 기관지천식 환자군의 기관지폐포세척액내 IL-10은 기관지폐포세척액이나 기관지 조직내 호산구 침윤과 역상관관계를 보였지만, 정상대조군과 비교해서 IL-10 감소가 관찰되지 않았기 때문에 기관지천식에서는 항염증 효과가 있는 IL-10이 중요하게 작용하지 않을 것으로 생각된다.

• BMB Reports
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• 제40권5호
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• pp.765-772
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• 2007

Eosinophils act as effectors in the inflammatory reactions of allergic diseases including atopic dermatitis. Atopic dermatitis patients and others with allergic disorders suffer from eosinophilia, an accumulation of eosinophils due to increased survival or decreased apoptosis of eosinophils. In this study, a differential phosphoproteome analysis of AML14.3D10 eosinophil cell line after treatment with IL-5 or dexamethasone was conducted in an effort to identify the phosphoproteins involved in the proliferation or apoptosis of eosinophils. Proteins were separated by 2-DE and alterations in phosphoproteins were then detected by Pro-Q Diamond staining. The significant quantitative changes were shown in nineteen phosphoproteins including retinoblastoma binding protein 7, MTHSP75, and lymphocyte cytosolic protein 1. In addition, seven phosphoproteins including galactokinase I, and proapolipoprotein, were appeared after treatment with IL-5 or dexamethasone. Especially, the phospho-APOE protein was down-regulated in IL-5 treated AML14.3D10, while the more heavily phosphorylated APOE form was induced after dexamethasone treatment. These phosphoproteome data for the AML14.3D10 cell line may provide clues to understand the mechanism of eosinophilia as well as allergic disorders including atopic dermatitis.

• 대한의생명과학회지
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• 제27권2호
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• pp.95-98
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• 2021

The S100 family proteins act as inducers of cancer cell apoptosis and inflammatory mediators. This study examined the pro-apoptotic mechanism caused by S100A8 and S100A9 in human FIP1L1-PDGFRα-positive eosinophilic leukemia cells. S100A8 and S100A9 elicited the death of EoL-1 cells in a time and dose-dependent manner. The activation of PDGFRα was suppressed by a decrease in PDGFRα after treatment with S100A8 and S100A9. Cycloheximide, a translation inhibitor, suppressed PDGFRα expression from 1 h to 5 h, and a co-treatment with S100A8 and S100A9 boosted the decrease in expression. The phosphorylation and expression of STAT5 decreased after treatment with S100A8 and S100A9 in EoL-1 and imatinib-resistant (EoL-1-IR) cells. S100A8 and S100A9 induced the chemotaxis of EoL-1 cells but did not affect the chemoattraction of EoL-1-IR. These findings indicate the cell death mechanism due to S100 family proteins and the development of leukemia therapy using S100A8 and S100A9.

• 대한임상검사과학회지
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• 제49권2호
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• pp.150-160
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• 2017

아토피피부염은 만성 염증성 피부질환으로 습진성병변, 피부건조 및 가려움증의 특징적 증상을 보이는 질환이다. 현재 사용되고 있는 아토피피부염 치료약제들은 오래 사용시 여러 부작용이 있어서 이를 대신할 새로운 대체 치료법의 개발이 요구되고 있다. Curcumin은 항염, 항알러지와 같은 효과를 나타내는 천연 폴리페놀(polyphenol)이며, 발광다이오드(light emitting diode, LED) 광치료는 아토피피부염과 상처치유에 효과가 있는 것으로 알려져 있다. 본 연구는 DNCB로 유도한BALB/c 마우스의 아토피피부염에서 curcumin 투여와 630 nm LED 조사를 병용하여 그 치료 효과를 높일 수 있는가를 조사하기 위해 시도하였다. 아토피피부염의 치료 효과를 조사하기 위해 modified SCORAD 지수, 조직병리학적 분석, 면역조직화학염색 및 TUNEL 검사를 사용하였다. 그 결과 curcumin 투여와 630 nm LED 조사가 각각 SCORAD 지수, 비만세포 및 탈과립세포의 수, 호산구 수, 표피세포의 증식능 및 자멸세포의 수를 의미 있게 감소시키고, 비만세포의 탈과립을 억제하여 섬유모세포에 의한 콜라겐 생성을 의미 있게 감소시켰으며, curcumin 투여와 LED 조사를 병용하였을 경우 단일 처리군에 비해 이들 수치가 의미 있게 감소하는 것을 확인하였다. 이러한 결과는 아토피피부염 치료에 curcumin 투여와 LED 조사가 각각 효과가 있음을 의미하며, 병용 치료 시 그 효과가 좀 더 향상된다는 것을 의미하는 것으로, 아토피피부염의 대체치료 전략으로 curcumin 투여와 630 nm 조사의 병용 치료를 제안한다.