• 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.

• 대한의생명과학회지
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• 제24권2호
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• pp.134-137
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• 2018

S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

• 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.

• 대한임상검사과학회지
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• 제49권2호
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• pp.128-134
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• 2017

Der p 1과 Der p 2는 알레르기 질환과 관련된 집먼지 진드기의 핵심적인 알러젠이다. 본 연구에서는 Der p 1과 Der p 2가 단구에서 S100A8과 S10A9을 분비시키는지를 확인하였고, 분비된 S100A8과 S10A9이 호중구의 세포고사 조절기전에 작용하는지를 연구하였다. Der p 1과 Der p 2는 정상인의 단구에서 S100A8과 S10A9을 유의하게 증가시켰고, S100A8과 S10A9은 정상인과 알레르기 질환 호중구의 자발적 세포고사를 억제 시켰다. 호중구의 Lyn, Akt, ERK는 S100A8과 S10A9을 시간별로 처리하였을 때 활성화하였다. 본 연구를 통하여 단구와 호중구에서 Der p 1과 Der p 2의 역할을 규명하였고, 나아가 관련된 알레르기 병인기전을 이해하는데 유용할 것이다.

• 대한의생명과학회지
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• 제26권3호
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• pp.226-229
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• 2020

S100A8 functions as an essential factor in inflammatory response. Cytokine release of monocytes and regulation of neutrophil apoptosis are important steps in pathogenesis of allergy. This study aims to examine the relation between cytokine release of monocytes due to S100A8 and neutrophil apoptosis. S100A8 enhanced the release of IL-6 and IL-8 in monocytes of normal and allergic subjects. Treatment of supernatants of normal and allergic monocytes with S100A8 blocked neutrophil apoptosis by inhibition of caspase 9 and caspase 3 activation. The secretion signal induced by S100A8 is involved in TLR4, Src family protein, PKCδ, ERK1/2, p38 MAPK, JNK, and NF-κB. These findings may contribute to understanding the complex pathogenesis of allergic diseases by determining inflammatory responses associated with S100A8, monocytes, and neutrophils.

• 대한의생명과학회지
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• 제19권4호
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• pp.344-347
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• 2013

The S100A8 and S100A9 proteins play important roles in inflammatory diseases. The house dust mite acts as a major allergen that induces allergic diseases. We investigated the effect of the house dust mite on S100A8 and S100A9 protein expression in monocytes. We also examined the effect of CCL2, a powerful monocyte chemoattractant, on the expression of both proteins. Extract of Dermatophagoides pteronissinus (DP), recombinant Der p 1 and Der p 2, or CCL2 had no effect on S100A8 and S100A9 expression in human monocytic THP-1 cells. Monocytes were isolated from healthy donors and treated with DP, Der p 1, and Der p 2. S100A8 expression in monocytes increased after a 24 h stimulation with DP, Der p 1, and Der p 2, and CCL2 also increased S100A8 production. However, S100A9 expression in monocytes was not altered by DP, Der p 1, Der p 2, or CCL2. These results indicate that house dust mite and CCL2 may trigger an inflammatory response by altering S100A8 expression.

• 대한의생명과학회지
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• 제21권2호
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• pp.122-125
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• 2015

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

• 대한의생명과학회지
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• 제22권2호
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• pp.60-64
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• 2016

In the pathogenesis of inflammatory diseases such as allergies, S100A8 acts as an important molecule and T lymphocytes are essential cytokine-releasing cells. In this study, we investigated the effect of S100A8 on release of cytokines, specifically MCP-1, IL-6, and IL-8 in T cells, and its associated signaling mechanism. S100A8 increased secretion of MCP-1, IL-6, and IL-8 in a time- and dose-dependent manner. Elevated secretion of MCP-1, IL-6, and IL-8 due to S100A8 was inhibited by the TLR4 inhibitor TLR4i, the PI3K inhibitor LY294002, the $PKC{\delta}$ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF-${\kappa}B$ inhibitor BAY-11-7085. S100A8 induced phosphorylation of ERK, p38 MAPK, and JNK in a time-dependent manner, and activation was suppressed by TLR4i, LY294002, and rottlerin. S100A8 induced NF-${\kappa}B$ activation by $I{\kappa}-B{\alpha}$ degradation, and NF-${\kappa}B$ activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, $PKC{\delta}$, MAPKs, and NF-${\kappa}B$ will contribute to elucidation of the S100A8-invovled mechanism.

• Applied Microscopy
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• 제47권4호
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• pp.233-237
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• 2017

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disease with an increased number of mature eosinophils and their precursors, which results in infiltration into organs and organ enlargement. The main cause of this disease is the overexpression of tyrosine kinase. However, there is a need for alternative medication, because some patients are resistant to imatinib, which is a tyrosine kinase inhibitor for leukemia. Many studies have indicated that S100A8 and splicing factor proline and glutamine-rich (SFPQ) function as initiation signals of apoptosis in CEL cells. We reviewed structural studies on CEL cells related to S100A8 and SFPQ. Particularly, this review highlighted microscopic results for the study of S100A8 and SFPQ in CEL cells.

• 한국응용과학기술학회지
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• 제36권1호
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• pp.1-12
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• 2019

돼지감자를 9번 찌고 9번 말려서 차를 제조한 다음 M사의 돼지감자차와 성분 및 기능성을 비교 분석하였다. 개발한 돼지감자차는 칼로리 342.27kcal, 탄수화물 73.87g/100g, 유리당 32.66mg/100g, 회분 6.80g/100g, 단백질 8.21g/100g이었고 무기물 총량은 2,785.67mg/100g, 칼륨 2,563.93mg/g, 칼슘 97.52mg/g, 마그네슘 88.78mg/g 등이었다. 돼지감자차의 유리당 총량은 32.66mg/100g이고 그중 fructose 17.40mg/100g, sucrose 9.03mg/100g, glucose 6.05mg/100g이었다. 돼지감자 차의 포화지방산은 30.34mg/100g, 4 불포화지방산은 69.66mg/100g이었고 그 중 linoleic acid 47.00mg/100g, palmitic acid 25.31mg/100g, linolenic acid 8.61mg/100g이었다. DPPH 라디컬 소거력은 개발한 차 34.2%, 비교용 M사차 5.2%, 지표물질 44.0%였다. ABTS 라디컬 소거력은 개발한 차 93.0%, M사차 61.9%, 지표물질 47.6%였다. SOD 유사활성은 개발한 차 2.7%, M사차 1.6%였다. 플라보노이드 함량은 개발한 차 2.8 fold, M사차 2.0 fold, 지표물질 1.7 fold 였다. 폴리페놀 함량은 개발한 차 38.2 fold, M사차 8.92 fold, 지표물질 14.0 fold였다. ${\alpha}$-Glucosidase 저해율은 개발한 차 9.83%, M사차 8.92%였다. 기호도는 1회 우린 것과 5회 우린 것을 비교하였다. 1회 우린 것을 기준으로 할 때 5회 우린 것의 기호도 중 색은 개발한 차 83.7%, 비교용 차 50.0%, 향기는 개발한 차 78.0%, 비교용 차 42.5%, 맛은 개발한 차 66.7%, 비교용 차 37.5%, 종합적인 기호도는 개발한 차 73.3%, 비교용 차 47.5%로 나타났다. 이같이 비교용 M사차는 우릴수록 추출 성분이 감소하여 5회 후에 종합적인 기호도는 46.3%로 감소한 반면 개발한 차는 감소폭이 적어서 73.3%를 나타냈다. 이같이 개발한 돼지감자차는 비교용 M사차 및 지표물질보다 항산화 작용이 강하고 유효 물질 함량도 더 많고, 기호성도 높으므로 질병 예방 및 개선 효과가 클 것으로 생각한다.