• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.837-845
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• 2014

Background: Overweight and obesity are recognized as major drivers of cancers including breast cancer. Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers, including breast cancer. Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. Materials and Methods: This study included 39 females with breast cancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profiles were determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures were also recorded for all participants. Results: IL-6, IL-12 and LCN2 were significantly higher in control obese and breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression was significantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positively correlated with obesity markers in all obese patients. Conclusions: Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management.

• Mass Spectrometry Letters
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• v.12 no.3
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• pp.66-75
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• 2021

Interleukin-4 (IL-4) and IL-13 are cytokines secreted by immune cells. Cytokines induce the proliferation of macrophages or promote the differentiation of secretory cells. The initiation and progression of allergic inflammatory diseases, such as asthma, are dependent on cytokines acting through related receptor complexes. IL-4 and IL-13 are N-glycoproteins. Glycan structures in glycoproteins play important roles in protein folding, protein stability, enzymatic function, inflammation, and cancer development. Therefore, the glycan structure of IL-4 and IL-13 needs to be elucidated in detail for the development of effective therapies. We report the first attempt to characterize the site-specific N-glycosylation of recombinant IL-4 and IL-13 via liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The tandem mass spectra of intact N-glycopeptides were identified using the Integrated GlycoProteome Analyzer (I-GPA) platform, which can automatically and rapidly analyze multiple N-glycopeptides, including their glycan composition and amino acid sequences. The recombinant IL-4 and IL-13 were identified with amino acid sequence coverages of 84% and 96%, respectively. For IL-4, 52 glycoforms on one N-glycosylation site were identified and quantified. In IL-13, 232 N-glycopeptides from three N-glycosylation sites were characterized, with the site Asn52 being the most extensively glycosylated (~80%). The complex glycans were the most abundant glycan on IL-4 and IL-13 (~96% and 91%, respectively), and the biantennary glycans were the most abundant in both recombinant IL-4 and IL-13 proteins.

• Journal of Periodontal and Implant Science
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• v.51 no.4
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• pp.254-263
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• 2021

Purpose: Periodontitis is associated with a dysbiosis of periodontopathic bacteria, which stimulate the interleukin (IL)-23/IL-17 axis that plays an essential role in the immunopathogenesis of this disease, leading to alveolar bone destruction through receptor activator of nuclear factor κB ligand (RANKL). IL-23 receptor mRNA (IL-23R) has been identified in periodontitis, and IL-17 receptor A mRNA (IL-17RA) and its protein have not yet been evaluated in patients with periodontitis. In this study was measure IL-23R and IL-17RA in gingival tissue (GT) from patients with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAP) and to explore correlations with clinical parameters. Methods: We included 16 healthy subjects (HS), 18 patients with GCP, and 14 with GAP. GT samples were collected during periodontal surgery. Both IL-23R and IL-17RA were detected by enzyme-linked immunosorbent assay. Results: The results were analyzed with Mann-Whitney U test and Spearman' rank correlation coefficients using SPSS version 25.0. We found lower IL-23R levels in patients with GCP and GAP than in HS. Contrarily, we observed higher IL-17RA levels in GCP and GAP patients than in HS. Moreover, we found negative correlations between IL-23R in GT and probing depth and clinical attachment loss (CAL). Likewise, a positive correlation of IL-17RA in GT with CAL was found. Conclusions: The results of these findings suggest that the reverse behavior between IL-23R and IL-17RA in periodontitis patients may also be involved with the activation of RANKL, which promotes alveolar bone loss.

• Biomedical Science Letters
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• v.24 no.2
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• pp.94-101
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• 2018

Tuberculosis (TB) is infectious disease caused by Mycobacterium tuberculosis (MTB) infection. It is known that not only the property of microorganism but also the genetic susceptibility of infected patients is controlled. Interleukin 2 (IL-2) is a cytokine belonging to type 1 T helper (Th1) activity. In addition, IL-2, when infected with MTB, binds IL-2 receptor and promotes T cell replication and is involved in granuloma formation. The aim of this study was to investigate the genetic polymorphisms of the IL-2 receptor gene in tuberculosis patients and normal individuals. We analyzed 22 SNPs in three genes using the genotype data of 443 tuberculosis cases and 3,228 healthy controls from the Korea Association Resource for their correlation with tuberculosis case. IL2RA, IL2RB, and IL2RG genes were genotyped of 16, 4, and 2 SNPs, respectively. Among three genes, only IL2RA gene polymorphisms showed statistically significant association with tuberculosis case. 6 SNPs with high significance were identified in the IL2RA gene. In addition, the linkage disequilibrium (LD) structure of IL2RA gene was confirmed. SNP imputation of IL2RA gene was performed, it was confirmed that more SNPs were significant between case and control. If we look at the results of IL2RA gene analysis above, we can see that genetic polymorphism in the gene expressing $IL-2R{\alpha}$ will regulate the expression level of $IL-2R{\alpha}$, and the change in the immune system involved in $IL-2R{\alpha}$. In this study, genetic polymorphism that may affect host immunity suggests that susceptibility to tuberculosis may be controlled.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9295-9300
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• 2014

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13-1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.549-564
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• 2022

BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.369-377
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• 2018

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

• Journal of Periodontal and Implant Science
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• v.50 no.2
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• pp.74-82
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• 2020

Purpose: The aim of this cross-sectional study was to investigate the effect of scaling and root planing (SRP) on the expression of anti-inflammatory cytokines (interleukin [IL]-4, IL-9, IL-10, and IL-13) in the gingival crevicular fluid (GCF) of electronic cigarette users and non-smokers with moderate chronic periodontitis (CP). Methods: Electronic cigarette users and non-smokers with CP were included in the study. Full-mouth plaque and gingival indices, probing depth (PD), clinical attachment loss (CAL), and marginal bone loss (MBL) were assessed. The GCF was collected, and its volume and levels of IL-4, IL-9, IL-10, and IL-13 were assessed. These parameters were evaluated at baseline and 3 months after SRP. The sample size was estimated, and comparisons between groups were performed. P<0.05 was considered to indicate statistical significance. Results: Thirty-six electronic cigarette users (47.7±5.8 years old) and 35 non-smokers (46.5±3.4 years old) with CP were included. At baseline, there were no differences in plaque index (PI), PD, CAL, MBL, and GCF IL-4, IL-9, IL-10, and IL-13 between electronic cigarette users and nonsmokers. At the 3-month follow-up, there were no significant differences in PI, gingival index (GI), PD, CAL, and MBL in electronic cigarette users compared to baseline, while there were significant reductions in PI, GI, and PD among non-smokers. At the 3-month follow-up, GCF IL-4, IL-9, IL-10, and IL-13 levels were significantly elevated in both groups (P<0.05) compared to baseline. The increases in GCF IL-4, IL-9, IL-10, and IL-13 levels were significantly higher in non-smokers (P<0.05) than in electronic cigarette users at the 3-month follow-up. Conclusions: Levels of GCF IL-4, IL-9, IL-10, and IL-13 increased after SRP in electronic cigarette users and non-smokers with CP; however, the anti-inflammatory effect of SRP was more profound in non-smokers than in electronic cigarette users.

• The Korean Journal of Pain
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• v.31 no.3
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• pp.206-214
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• 2018

Background: Immune responses appear to be affected by anesthetics and analgesics. We investigated the effects of caudal tramadol on the postoperative immune response and pain management in pediatric patients. Methods: Sixty ASA-I pediatric patients aged 3-10 years undergoing lower abdominal surgery. Patients were randomly assigned either to a caudal bupivacaine (0.25%) group (group B), or a group that received caudal tramadol (1 mg/kg) added to the bupivacaine (0.25%) (group T). Both were diluted in a 0.9% NaCl solution to a total volume of 1ml/ kg. The systemic immune response was measured by collecting blood samples preoperatively, at the end of anesthesia, and at 24 and 72 hours postoperatively, and studied for interleukin IL-6, C-reactive proteins (CRP) cortisol levels, and leucocytes with its differential count. Postoperative pain was assessed along with sedation scales. Results: Postoperative production of IL-6 was significantly higher in group B at the end of anesthesia, than at the $24^{th}$ hour, and at the $72^{nd}$ hour in group B and group T, respectively. The immune response showed leukocytosis with increased percentages of neutrophil and monocytes, and a decreased lymphocyte response rate within both groups with no significant differences between the groups. Cortisol and CRP were significantly higher in group B. Conclusions: Adding tramadol to a caudal bupivacaine block can attenuate the pro-inflammatory cytokine response, Cortisol, and CRP in children undergoing lower abdominal surgery.

• The Korea Journal of Herbology
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• v.31 no.1
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• pp.69-75
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• 2016

Objectives : The aim of this study is to investigate the various effects of individual or combined extract of GamiSaengmaeksan (GSS) on cell viability, anti-inflammatory and antioxidant activityMethods : In order to evaluate cytotoxicity, MTT assay was performed. We investigated the levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 and interleukin (IL)-1β, and nitric oxide(NO) in LPS-induced RAW 264.7 cells to check the effects on anti-inflammatory activity. The level of NO production in RAW 264.7 cells was measured by using Griess reagent. The levels of cytokines and ROS were measured by Luminex and Flow cytometry, respectively.Results : At concentration of 200 ㎍/㎖ GSS, cytotoxicity was observed in RAW 264.7 cells. However, at concentration less than 100 ㎍/㎖ of both combine and individual GSS, cytotoxicity was not observed in Raw 264.7 cells. However, the level of ROS in RAW 264.7 cells were decreased at both extract of 100 ㎍/㎖ GSS. Also, the level of NO in RAW 264.7 cells were decreased from extraction of concentration of 100 ug/ml in GSS and individual-extraction of Liriopis Tuber, White Ginseng and Glycyrrhizae Radix. In addition, productions of pro-inflammatory cytokines (TNF-α) in LPS-induced RAW 264.7 cells were decreased from extraction of concentration of 10 and 100 (㎍/㎖) in GSS and individual-extraction of Liriopis Tuber.Conclusions : It is concluded that combined extract of GSS appears to be more effective in anti-oxidation and anti-inflammatory effect than those in individual-extraction of GSS. These results may be developed as a raw material for new therapeutics to ease the symptoms related with inflammatory and oxidative stress.