• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8775-8778
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• 2014

Background: To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer. Materials and Methods: A total of 113 silicosis patients and 116 workers without silicosis were enrolled in the case-control study. IL-17A A-832G and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%, 8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found. The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of combined effects showed that the individuals with GG+AG genotype of IL-17A and GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). Conclusions: IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may have a protective effect. No relationship was found between IL-17A gene polymorphisms at A-832G and silicosis.

• BMB Reports
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• v.44 no.5
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• pp.335-340
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• 2011

In this study, we attempted to isolate novel mast cell-stimulating molecules from Staphylococcus aureus. Water-soluble extract of S. aureus cell lysate strongly induced human interleukin-8 in human mast cell line-1 and mouse interleukin-6 in mouse bone marrow-derived mast cells. The active molecule was purified to homogeneity through a $C_{18}$ reverse phase HPLC column. By determination of its structure by MALDITOF and $^1H$- and $^{13}C$-NMR, adenosine was revealed to be responsible for the observed cytokine induction activities. Further studies using 8-sulfophenyl theophylline, a selective adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureus-engulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel view of the source of exogenous adenosine in vivo and provide a mechanistic link between inflammatory disease and bacterial infection.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• Journal of Microbiology and Biotechnology
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• v.33 no.7
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• Food Science of Animal Resources
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• v.43 no.5
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• pp.859-876
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• 2023

It is known that animal-origin medicine could be one of effective treatment to remedy atopic dermatitis (AD) by controlling the cytokines. Cicadidae Periostracum (CP), the slough of Cryptotympana pustulata, has been frequently used for treating AD and skin affliction in traditional Korean Medicine. This study is aimed at investigating the ameliorating effects of CP on AD and its potential mechanism. The dinitrochlorobenzene sensitized mice were treated with CP for 2 weeks. The various biomarkers and the dermatitis scores presented that CP treatment can induce the visual and biological improvements of AD model. Pruritus, the most serious symptom of AD, which can cause repeated scratching behaviors and finally lead to lichenification, was reduced with CP treatment by regulating the inflammatory reactions. In addition, CP treatment diminished the number of mast cells that are known for causing inflammatory reactions. Moreover, it is proven that CP can decline secretion of interleukin-22, which means CP treatment has anti-inflammatory effects. CP treatment can correct the imbalance of helper T (Th)1 and Th2, downregulating thymic stromal lymphopoietin that leads to decrease of mRNA level of inflammatory cytokines. The crucial role of CP treatment is controlling of the Janus kinase 1/signal transducer and activator of transcription 3 pathway. In addition, CP treatment has the inhibitory effects on kallikrein related peptidase (KLK) 5 and KLK7. Taken together, CP treatment can ameliorate most symptoms and problems caused by AD disease, improving the AD patients' life quality.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.738-744
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• 2013

The purpose of this study is to investigate effects of White Ginseng-Ejung-tang water extract (EJ) on production of various cytokines such as interleukin (IL)-2, IL-5, IL-6, IL-10, IL-12p70, macrophage inflammatory protein (MIP)-2, vascular endothelial growth factor (VEGF), keratinocyte-derived chemokine(KC), tumor necrosis factor (TNF)-${\alpha}$, and granulocyte macrophage colony-stimulating factor (GM-CSF) in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Levels of cytokines were measured by High-throughput multiplex bead array cytokine assay based on xMAP (multi-analyte profiling beads) technology. EJ significantly decreased levels of IL-2, IL-12p70, IL-5, MIP-2 for 24 h incubation at the concentrations of 25, 50, and 100 ${\mu}g/mL$ in LPS-induced RAW 264.7 (P < 0.05). EJ significantly decreased levels of IL-6 at the concentrations of 50 and 100 ${\mu}g/mL$ (P < 0.05). EJ significantly decreased levels of IL-10 and VEGF at the concentrations of 25 and 100 ${\mu}g/mL$ (P < 0.05). EJ significantly decreased levels of KC at the concentrations of 100 ${\mu}g/mL$ (P < 0.05). EJ did not show any significant effect on TNF-${\alpha}$ and GM-CSF production. These results suggest that EJ has anti-inflammtory property related with its inhibition of IL-2, IL-5, IL-6, IL-10, IL-12p70, MIP-2, VEGF, and KC production in LPS-induced macrophages.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.795-801
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• 2013

The purpose of this study is to investigate effects of White Ginseng-Ejung-tang (EG) and Red Ginseng-Ejung-tang (ER) water extract on production of various cytokines such as interleukin (IL)-21, IL-25, IL-$28{\beta}$, erythropoietin (EPO), Exodus-2, monocyte chemotactic protein (MCP)-5, macrophage inflammatory protein (MIP)-$3{\alpha}$, MIP-$3{\beta}$, Fractalkine, and TARC in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Levels of cytokines were measured by High-throughput multiplex bead array cytokine assay based on xMAP (multi-analyte profiling beads) technology. ER significantly decreased levels of IL-21, IL-25, IL-$28{\beta}$, EPO, Exodus-2, MCP-5, MIP-$3{\alpha}$, MIP-$3{\beta}$, TARC, and fractalkine for 24 h incubation at the oncentrations of 25 and 100 ${\mu}g/mL$ in LPS-induced RAW 264.7 (P < 0.05). But EG did not show any significant effect. These results suggest that ER has anti-inflammtory property related with its inhibition on the production of IL-21, IL-25, IL-$28{\beta}$, and chemokines such as EPO, MCP-5, MIP-$3{\alpha}$, MIP-$3{\beta}$, Fractalkine, Exodus-2, and TARC in LPS-induced macrophages.

• Korean Journal of Food Science and Technology
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• v.48 no.4
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• pp.392-397
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• 2016

Zaluzanin C is a sesquiterpene lactone isolated from Ainsliaea acerifolia, a Korean medicinal plant. In the present study, the anti-inflammatory effects of zaluzanin C were demonstrated in lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7 cells). Zaluzanin C inhibited the release of nitric oxide (NO) by alleviating the protein expression of inducible NO synthase in LPS-treated RAW264.7 cells. Furthermore, it suppressed the release of interleukin-6 induced by LPS. Zaluzanin C was also found to block the translocation of the p65 subunit of nuclear factor-kB from the cytosol to the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of zaluzanin C. These data suggest the potential of zaluzanin C in the treatment of inflammatory diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4977-4982
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• 2016

Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.