• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Journal of Life Science
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• v.21 no.9
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• pp.1259-1265
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• 2011

The purpose of this study was to determine whether a single bout of aerobic exercise affects the expression level of toll-like receptor4 (TLR4), IL-6, TNF-${\alpha}$, and suppressor of cytokine signaling-3 (SOCS-3) expression in rat hindlimb muscles depending on fiber types. To accomplish this, thirteen 7-wk Balb/c male mice were randomly assigned to an experimental group or a control group. The exercise protocol consisted of a single bout of treadmill exercise (inclination $10^{\circ}$, speed 17 cm/sec 10 min, 33 cm/sec 10 min, 50 cm/sec) and the animals were killed 24 hr after the exhaustion protocol. The level of TLR4, IL-6, TNF-${\alpha}$, and SOCS-3 mRNA expression was measured by quantitative real-time PCR in soleus and plantaris muscles. A single bout of aerobic treadmill exercise increased TLR4 mRNA expression in the soleus muscle (p<0.05), whereas plantaris TLR4 mRNA expression did not change. Additionally, acute exercise led to a significant increase in IL-6, TNF-${\alpha}$, and SOCS-33 mRNA in the soleus muscle, while transcripts of these genes were not affected by exercise in the plantaris muscle. In conclusion, expression level of several immune-related genes such as TLR4, cytokines, and SOCS-3 is regulated by acute exercise in a fiber type specific manner.

• Applied Microscopy
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• v.31 no.3
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• pp.275-285
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• 2001

The pulmonary alveolar macrophage is thought to play an important role in the mediation of acute inflammatory lung injury by secretory products including degraded enzymes, cytokines, and reactive oxygen metabolites . This study was conceived to understand the role of alveolar macrophage in oxidative stress induced acute lung injury. To examine the alveolar macrophages and xanthine oxidase (XO) activity in bronchoalveolar lavage fluid (BALF), time-dependent changes of numbers of alveolar macrophages, monocytes and neutrophils in alveolar cavity were counted in association with ultrastructural and cytochemical observations of lung tissue and alveolar cells. The number of monocytes was increased (p<0.001) at 1h after IL-1 treatment compared with that of sham. At 2h after instillation of IL-1, the number of alveolar macrophages was the highest, XO activity in BALF was elevated at 2h after IL-1 instillation and the activity was markedly elevated(p<0.05) at 3h after IL-1 treatment. On the basis of these experimental results, it is suggested that, during early phase of acute lung injury induced by IL-1, alveolar macrophage-derived XO contributes to lung injury earlier than the neutrophilic respiratory burst.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.54-59
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• 2007

In this paper, we present evidence that the Korean red ginseng extract shows the immunomodulatory activities during postoperative chemotherapy after curative surgery in patients with advanced colon cancer. We measured the circulating interleukin-2 (IL-2), interleukin-8 (IL-8)and interleukin-10 (IL-10) as a immune modulator to evaluate the effect of Korean red ginseng. The mean preoperative value of IL-2 was similar in the non-RG group and the RG group (5.72 pg/ml versus 6.87 pg/ml, p>0.05). The mean value of IL-2 was compared with IL-2 from healthy control group, there was no significant difference (14.89 pg/ml versus 14.22 pg/ml, p>0.05). The mean preoperative value of IL-8 was higher in the non-RG group comparing with the RG group (30.92 pg/ml versus 36.25 pg/ml, p < 0.05). At postoperative 3 month, the mean values of IL-8 from non-RG and RG group down to 24.56 pg/ml and 21.46 pg/ml respectively. The IL-8 of RG group at 3 month showed no difference with that of HC group(21.46 pg/ml versus 16.31 pg/ml, p>0.05). The preoperative mean value of IL-10 of non-RG, RG and HC group was 11.56 pg/ml, 10.8 pg/ml, and 3.68 pg/ml respectively. At postoperative 3 month, the mean values of IL-10 from non-RG and RG group down to 8.45 pg/ml and 5.04 pg/ml respectively. In spite of decreasing IL-10 levels of both cancer Patients group with time, there was still significant difference with that of HC group (non-RG versus HC group, p=0.00, RC versus HC group, p=0.04). The results of this study suggest that the red ginseng extract may have some immunomodulatory properties associated with IL-2, IL-8 and IL-10 activity in patients with advanced colorectal cancer during postoperative chemotherapy. We think to need the further studies and a larger sample size to fully evaluate the antitumor effect of ginseng and need to establish this mechanism of action as well as identify the active components associated with antitumor activity and immunomodulation in patients with advanced colorectal cancer.

• BMB Reports
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• v.35 no.6
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• pp.623-628
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• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2439-2442
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• 2013

We investigated the possible association of interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 patients and 137 healthy controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The IL-10 mRNA expression of AML patients and controls with different genotype was detected by real-time quantitative polymerase chain reaction (RT-PCR). Genetic analysis of IL-10 revealed that the -819AA genotype frequencies and the -819A allele frequencies in the AML group were higher than in the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in the AML group (75.6% vs 63.9%, P<0.05). IL-10 mRNA expression in incipient AML patients was obvious higher than the non-tumor group and the remission group ($7.78{\times}10^{-3}$ vs $2.43{\times}10^{-3}$, $3.64{\times}10^{-3}$, P<0.05).The study suggested that the haploid TA and genotype TA/TA may be associated with AML in Han people in Hunan province.The IL-10 SNPs at -819 and -592 sites were associated with AML and may affect IL-10 mRNA expression in AML patients.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.57-67
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• 2000

Currently asthma is considered to be an inflammatory disease characterized by airway hyperresponsiveness and pulmonary eosinophilia, and mediated by Th lymphocytes expressing a Th 2 cytokine pattern. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objectives: We aimed to identify the effect of Haepyoijin-tang on the transcriptional activities of cytokines involved in the asthma model. Materials and Methods: RBL-2H3 cell lines were used. Cells were stimulated with DNP-IgE or Calcium inophore+PMA for maximal gene expression. After 24 hours of Haepyoijin-tang-treatment, total cellular RNAs were collected using the Trizol solution method. Then the transcriptional activities of cytokines(IL-1, 4, 5, 10, 13, $TNF-{\alpha}$) were measured by RT-PCR with electrophoresis. Results: DNP-IgE and Calcium inophore+PMA induced IL-4/IL-5 production separately peaked at 3 hours after the stimulation, but the efficacy was better in the Calcium inophore+PMA group. In the IL-4 study, sample groups of 10%, 1 %, 0.01 % Haepyoijin-tang-treatment showed 83%, 98%, 96% of transcriptional activities compared to the control group. In the IL-5 study, sample groups of 10%, 1%, 0.1 %, 0.01 % Haepyoijin-tang showed 97%, 99%, 99%, 99% of transcriptional activities compared to the control group. In other studies any result was not obtained. Conclusions: This study shows that Haepyoijin-tang has an inhibitory effect on the transcription of IL-4 and IL-5 gene expression in RBL-2H3 cell lines. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.45-49
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• 1987

Employing the approach to isolate the genes expressed preferentially in cytolytic T cell (CTL) but not in other types of cell, 3 CTL-specific cDNAs were recently cloned. To characterize these cDNA clones in relation to CTL activation, their expression pattern after T cell antigen receptor (TCR) or interleukin 2 (IL-2) stimulation were investigated by RNA blot analysis of cloned CTL L3 cells. Transcripts level of two cDNA clones were markedly elevated by TCR stimulation but not by IL-2. In addition, transcripts expression of both clones were abrogated by cyclosporin A treatment. These results indicated that gene activation mediated by TCR is distinct from that mediated by IL-2 and imply that those two unidentified cDNA clones are related to TCR-mediated, IL-2-independent but cyclosporin A-sensitive pathway for CTL activation.

• The Journal of Internal Korean Medicine
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• v.45 no.3
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• pp.508-518
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• 2024

Objectives: To report a correlation of IL-6 of pancreatic cancer and cancer progression in three pancreatic cancer patients. Method: Three pancreatic cancer patients were monitored for changes in IL-6 levels, tumor markers (CEA, CA19-9), and clinical outcomes over their treatment period. Results: Patient 1's IL-6 levels rose with liver metastasis and tumor progression, coinciding with increases in tumor markers. Patient 2's IL-6 levels remained elevated during chemotherapy, correlating with tumor growth. Patient 3's IL-6 levels spiked prior to cancer progression. Conclusion: Elevated IL-6 levels were observed in advancing pancreatic cancer patients, suggesting IL-6 as a potential biomarker for monitoring cancer progression in pancreatic cancer. Regular IL-6 monitoring could improve prognostic evaluations and treatment strategies.

• Korean Journal of Acupuncture
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• v.35 no.2
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• pp.91-97
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• 2018

Objectives : This study was performed to investigate immune regulatory effects of the pharmacopuncture with MOK on hyperthyroid rats. Methods : The experimental hyperthyroidism was prepared by the intraperitoneal injection of L-thyroxine(LT4, 0.5 mg/kg) once daily for 2 weeks in Sprague-Dawley(SD) rats. The pharmacopuncture with MOK extract(MOK pharmacopuncture) at doses of 0.3 or 3 mg/kg was injected on acupuncture points in the thyroid glands of hyperthyroid rats once a day for 2 weeks. Propylthiouracil(PTU, 10 mg/kg) as a reference group was subcutaneously injected into the dorsal neck. We measured the levels of $IFN-{\gamma}$ and IL-4 in the sera of rats using enzyme-linked immunosorbant assay(ELISA) and determined the expression of $IFN-{\gamma}$, IL-4, IL-10, and Foxp3 in spleen tissues by reverse transcriptase-polymerase chain reaction(RT-PCR). Results : The treatment of MOK pharmacopuncture in hyperthyroid rats significantly decreased the serum levels of Th1 cytokine, $IFN-{\gamma}$(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU) and significantly increased the levels of Th2 cytokine, IL-4(p<0.05 for MOK 0.3 mg/kg, p<0.001 for MOK 3 mg/kg, and p<0.05 for PTU) compared to control group. Also, the MOK pharmacopuncture significantly increased IL-4 expression(p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU), IL-10(p<0.05 for MOK 3 mg/kg, and p<0.01 for PTU), and Foxp3(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg and p<0.01 for PTU) in spleen tissues of hyperthyroid rats compared to control group. Conclusions : Our results suggest that MOK pharmacopuncture can help to ameliorate the pathological progression of hyperthyroidism by regulation of the Th1/Th2 imbalance.