• 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.

• Parasites, Hosts and Diseases
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• v.51 no.1
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.79-81
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• 2008

The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol ($1{\sim}100$ mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN -induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-${\alpha}$, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.1
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• pp.149-154
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• 2003

The immunomodulatory activity of PJ-P, a polysaccharide fraction extracted from Paeonia japonica, were reported in our previous paper. In the present study, we investigated that PJ-P inhibited cancer growth through activation of macrophages. The activities of peritoneal macrophage to induce tumor necrosis factor (TNF)-$\alpha$, interleukin-1 (IL-1)$\beta$, interleukin-6 (IL-6) and interleukin-12 (IL-12) as well as to ingest fluorescence-latex microbeads were enhanced by treatment of PJ-P. Direct cytocidal activity of PJ-P against cancer cells was not shown. However, in vitro, peritoneal macrophages treated with PJ-P had an activity to kill cancer cells. Furthermore, PJ-P significantly prolonged the survival of mice implanted intraperitoneally with B16F0 mel-anoma cells. These results suggest that PJ-P could be a useful immunomodulator and assistant of anti-tumor agent.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.65-72
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• 2018

The purpose of this study was to investigate probiotic characteristics and immune enhancing effects of Bifidobacterium (B.) longum KBB1-26 and BIF-4, B. breve KBB5-22 isolated from human intestine for probiotic use in humans and animals. We measured acid, bile and heat tolerance, antimicrobial activity against pathogenic bacteria, Escherichia (E.) coli, Salmonella (S.) Enteritidis, Staphylococcus (S.) aureus, and Listeria (L.) monocytogenes. Immune enhancing effects of B. longum and B. breve were investigated by measuring nitric oxide (NO), nuclear factor ($NF-{\kappa}b$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in RAW 264.7 cells or RAW BLUE cells. B. longum KBB1-26 was survived at pH 2.0. B. longum KBB1-26 and BIF-4, B. breve KBB5-22 also showed tolerance to 0.3% of oxgall bile salt. B. longum KBB1-26 was able to survive at $70^{\circ}C$ and $80^{\circ}C$ for 20 min. KBB1-26 showed the antimicrobial inhibition zone to pathogenic bacteria such as E. coli (12 mm), S. Enteritidis (14 mm), S. aureus (14 mm) and L. monocytogenes (41 mm). The production of NO ($4.5{\pm}0.00{\mu}M/mL$) and $IL-1{\beta}$ ($39.7{\pm}0.55pg/mL$) of KBB1-26 significantly higher than BIF-4 and KBB5-22, respectively. In addition, KBB1-26 and KBB5-22 induce the production of high level of $TNF-{\alpha}$ and IL-6 in macrophages. Collectively, B. longum KBB1-26 have acid, bile, heat tolerance, antimicrobial activity and immune enhancing effects. These results suggest that KBB1-26 can be used as probiotics for humans and animals.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.1
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• Childhood Kidney Diseases
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• v.22 no.1
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• pp.22-27
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• 2018

Purpose: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

• Journal of Microbiology and Biotechnology
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• v.2 no.2
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• pp.135-140
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• 1992

The partitioning of recombinant human interleukin-2(rhII-2) in PEG 8000-dextran 38800 aqueous two-phase system has been investigated using three different sources of rhIL-2. In the case of pure rhIL-2, the solubility in a PEG-dextran two-phase system was low and most of rhIL-2 was partitioned into the bottom phase. For the recovery of rhIL-2 from insoluble protein aggregates, the inclusion bodies of recombinant E. coli were solubilized by the treatment with sodium dodecyl sulfate (SDS). The addition of SDS significantly enhanced not only the solubility of rhIL-2 but also the partitioning of rhIL-2 to the top phase. When the ratio of SDS to rhIL-2 was 2.0, the partition coefficient(K) and the recovery yield(Y) at the top phase were 4.5 and 88%, respectively, at pH 6.8. In order to reduce the recovery steps further, SDS was directly added to the intact recombinant E. coli cells and then partitioned into the PEG/dextran aqueous two-phase system. The observed partition coefficient ($K{\cong{3.0$) and recovery yield ($Y{\geq}80%$ )of this method were comparable to the rhIL-2 recovery from insoluble protein aggregates. The results obtained in this work indicate that PEG-dextran two-phase partitioning might provide a simple way for the recovery and partial purification of recombinant proteins which are produced as inclusion bodies.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1109-1114
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• 2021

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.