• Biomedical Science Letters
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• v.27 no.2
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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.

• Biomedical Science Letters
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• v.24 no.2
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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.

• Biomedical Science Letters
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• v.23 no.1
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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.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.128-134
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• 2017

Der p 1 and Der p 2 are essential allergens of house dust mite associated with the development of asthma. In the present study, we examined whether Der p 1 and Der p 2 induce a release of S100A8 and S100A9 in monocytes, which are involved in the regulatory mechanism of neutrophil apoptosis. We found that Der p 1 and Der p 2 significantly increased the secretion of S100A8 and S100A9 in normal monocytes. Moreover, S100A8 and S100A9 strongly suppressed the spontaneous apoptosis of normal and asthmatic neutrophils. The inhibitory effect of S100A9 was stronger than that of S100A8, and asthmatic neutrophils showed a higher inhibitory effect than normal neutrophils. S100A8 and S100A9 induced activation of Lyn, Akt, and ERK in a time-dependent manner. These findings elucidate the roles of Der p 1 and Der p 2 in the interaction between monocytes and neutrophils, as well as contributing to our knowledge of the pathogenesis of allergic diseases.

• Biomedical Science Letters
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• v.26 no.3
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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.

• Biomedical Science Letters
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• v.19 no.4
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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.

• Biomedical Science Letters
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• v.21 no.2
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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.

• Biomedical Science Letters
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• v.22 no.2
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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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• v.47 no.4
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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.

• Journal of the Korean Applied Science and Technology
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• v.36 no.1
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• pp.1-12
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• 2019

After making tea by steaming the Artichoke(Hellanthus tuberosus) nine times and drying them nine times, the ingredients and functions of the Artichoke tea were compared to those of M. It had 342.27kcal/100g in its own deloped Artichoke tea, 73.87g/100g of carbohydrates, 6.80g/100g of crude ash and 8.21g/100g of crude protein. The total of free sugars were 32.66mg/100, among them, fructose 17.40, sucrose 9.03 and glucose 6.05 mg/100g. The total mineral contents of the developed tea was 2,785.67mg/100g. It was 2,563.93mg/100g of potassium, 97.52mg/100g of calcium and 88.78mg/100g of magnesium. The saturated fat of Artichoke tea was 30.34mg/100g and unsaturated fat was 69.66mg/100g, among which the linoleic acid was 47.0mg/100%, palmitic acid was 25.31mg/100% and linolenic acid was 8.61mg/100g. DPPH radical scavenging was 34.2% of teas that were developed, 5.2% of M's for comparison, and 44.0% of index materials. ABTS radical scavenging was 93.0% of teas developed, 61.9% of M's tea and 47.6% of index materials, and SOD like activity was 2.7% of teas developed and 1.6% of M's tea. The flavonoid content was 2.8 fold of the tea developed, 2.0 fold of M's tea and 1.7 fold of index material. The polyphenol content was 38.2 fold, 8.92 fold of M's tea and 14.0 fold of index material. The inhibition rate for ${\alpha}$-glucosidase was 9.83% teas developed and 8.92% of M's. The sensory evaluation compares to the one time extract and the five time extract. Based on the one-time extract, color of tea developed was 83.7%, the M's tea was 50.0%, the flavor was 78%, M's tea was 42.5%, the delicate taste was 66.7% of teas developed and M's tea was 37.5% and the overall acceptability was 73.3% of teas developed, M's tea was 47.5%. The comparison of M's tea showed that the extract decreased as we made it, and the overall symbol level decreased to 46.3% after five time-extyracts, while that of the developed tea decreased to 73.3%. The Artichoke tea developed this way is believed to have greater antioxidant function, higher effective substance content, and a higher affinity than M's tea an index material for comparison purposes.