• Archives of Pharmacal Research
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• v.29 no.11
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• pp.969-976
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• 2006

Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.6
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• pp.263-267
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• 2007

We have previously demonstrated that the level of leukocytes and neutrophils significantly increased immediately and 30 min after exercise. Interleukin-8 (IL-8) is an inflammatory cytokine that acts as a chemokine on neutrophils. In the present study, we evaluated the correlation between the number of neutrophils and leukocytes, and between the number of neutrophils and plasma IL-8 level. Long-distance trained runners (TRs, n = 10) and untrained sedentary control subjects (SEDs, n = 10) ran for one hour at 70% of heart rate reserve. In the TR, the number of neutrophils correlated significantly with the number of leukocytes in the blood. However, there was no correlation between the number of neutrophils and the plasma IL-8 concentration in both groups. Expressions of IL-8 protein and mRNA were markedly higher in the TRs as compared to the SEDs at three time intervals (pre-exercise, immediately after exercise, and post exercise). In conclusion, our results show that 1) the neutrophil level was dependent on the level of leukocytes 2) there was no correlation between the neutrophils count and plasma IL-8 concentration and 3) a higher plasma IL-8 level in athletes may be a unique characteristic of intensive training.

• Safety and Health at Work
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• v.1 no.1
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• pp.69-79
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• 2010

Objectives: Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers' pneumoconiosis (CWP). Methods: To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-${\alpha}$) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic curve assessed the biomarker potential of each cytokine. Results: The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-${\alpha}$ level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-${\alpha}$ (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-${\alpha}$ were 11.63 pg/mL(sensitivity, 69%; specificity, 64%) and 4.52 pg/mL (sensitivity, 67%; specificity, 79%), respectively. Conclusion: The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-${\alpha}$ are associated with the progression of CWP.

• Clinics in Shoulder and Elbow
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• v.25 no.4
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• pp.296-303
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• 2022

Background: A previous study reported that hyperlipidemia increases the incidence of tears in the rotator cuff tendon and affects healing after repair. The aim of our study was to compare the gene and protein expression of torn rotator cuff tendons in patients both with and without hypercholesterolemia. Methods: Thirty patients who provided rotator cuff tendon samples were classified into either a non-hypercholesterolemia group (n=19, serum total cholesterol [TC] <200 mg/dL) and hypercholesterolemia group (n=11, serum TC ≥240 mg/dL) based on their concentrations of serum TC. The expression of various genes of interest, including COL1A1, IGF1, IL-6, MMP2, MMP3, MMP9, MMP13, TNMD, and TP53, was analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot analysis was performed on the proteins encoded by interleukin (IL)-6 and TP53 that showed significantly different expression levels in real-time qRT-PCR. Results: Except for IGF1, the gene expression levels of IL-6, MMP2, MMP9, and TP53 were significantly higher in the hypercholesterolemic group than in the non-hypercholesterolemia group. Western blot analysis confirmed significantly higher protein levels of IL-6 and TP53 in the hypercholesterolemic group (p<0.05). Conclusions: We observed an increase in inflammatory cytokine and matrix metalloproteinase (MMP) levels in hypercholesterolemic patients with rotator cuff tears. Increased levels of IL-6 and TP53 were observed at both the mRNA and protein levels. We suggest that the overexpression of IL-6 and TP53 may be a specific feature in rotator cuff disease patients with hypercholesterolemia.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.89-89
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• 2002

In this study, we examined transmission efficiency and expression level of the transgenes in the transgenic mice. The transgenic lines secreting a considerable amount of human lactoferrin(LF) thrombopoietin(TPO), interleukin-10(IL-10) into their milk were subjected to access the inheritance and maintenance of transgenic phenotype. They were bred through three generations. The transmission frequency for each generations(F9, F10, F11) of 3 lines was 38.03±10.43%(13/35), 48.33±3.76%(19/39) and 31.83±8.88%(9/28) in the LF line, 51.33±18.98%(20/38), 63.70±35.71%(12/20) and 29.57± 15.05%(8/26) in the TPO line, 38.27±17.74%(15/37), 47.47±29.88%(14/28) and 50.87±5.85%(14/28) in the IL-10 line, respectively. (omitted)

• Journal of Microbiology and Biotechnology
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• v.14 no.4
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• pp.810-815
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• 2004

Many biological properties and the clinical potential of human interleukin-2 (hIL-2) draw much attention to its high-level expression in mammalian cells. Recombinant human IL-2 (rhIL-2) was expressed in Chinese hamster ovary (CHO) cells, using the recently developed expression system which confers position-independent expression. Stable CHO cell lines carrying several hundred amplified copies of the rhIL-2 gene were easily obtained and rhIL-2 was expressed at high levels after selection with increasing concentrations of methotrexate. Interestingly, the insertion of the transcription terminator of the human gastrin gene into the downstream region of the gene for rhIL-2 considerably increased rhIL-2 expression. Using the expression system with the transcription terminator, it was possible to get a CHO cell line expressing the rhIL-2 at a very high level, about $11.4\mug/10^6$ cell/day, which is about 6 times higher than that previously reported. The biological activity of the rhIL-2 protein purified from the cell line was also confirmed by the cell proliferation assay.

• Journal of Pharmacopuncture
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• v.15 no.1
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• pp.7-11
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• 2012

Aim: Historically, mineral compound herbal medicines have long been used in treatments of immune-related diseases in Korea, China and other Asian countries. In this study, we investigated the anti-inflammatory effect of egg white combined with chalcanthite (IS4) on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: RAW 264.7 cells cultured with LPS and various concentrations of IS4 were analyzed to determine the production of pro-inflammatory cytokines and mediators by using enzyme-linked immune sorbent assays (ELISAs). Results: IS4 concentration inhibited the production of interleukin-1beta (IL-$1{\beta}$), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced by LPS. IS4 at high concentrations (25 and 50 ${\mu}g/ml$) inhibited, in concentration-dependent manner, the expression of tumor necrosis factor-alpha (TNF-${\alpha}$) stimulated by LPS. Conclusion: IS4 has shown an anti-inflammatory effect in RAW 264.7 cells.

• IMMUNE NETWORK
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• v.11 no.3
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• pp.169-174
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• 2011

Background: NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods: We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results: We investigated whether NOX2-deficiency affects T cell-mediated airway inflammation. Ovalbumin injection which activates T cell-mediated allergic response increased airway inflammation in wild-type mice, as evidenced by increased immune cell infiltration, allergic cytokine expression, and goblet cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more susceptible to allergen-induced lung inflammation compared to wild-type mice. Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion was substantially increased in deficiency of NOX2. Furthermore, inflammatory allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in accordance with enhanced generation of inflammatory cytokines interleukin-17 and interferon-${\gamma}$ by CD4+ T cells. Conclusion: These results indicate that NOX2 deficiency favorably produces inflammatory cytokines by T cells and thus increases the susceptibility to severe airway inflammation.

• 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.

• Nutrition Research and Practice
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• v.11 no.2
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• pp.90-96
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• 2017

BACKGROUND/OBJECTIVES: Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS: Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and $30{\mu}M$ lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B ($NF-{\kappa}B$), inhibitor kappa B ($I{\kappa}B$), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were determined via enzyme-linked immunosorbent assays. RESULTS: In cells treated with lycopene and LPS, the mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of $PGE_2$ and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of $NF-{\kappa}B$ and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS: Lycopene restrains $NF-{\kappa}B$ and JNK activation, which causes inflammation, and suppresses the expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.