• Title/Summary/Keyword: IL-17R

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Inverse behavior of IL-23R and IL-17RA in chronic and aggressive periodontitis

  • Ruiz-Gutierrez, Alondra del Carmen;Rodriguez-Montano, Ruth;Pita-Lopez, Maria Luisa;Zamora-Perez, Ana Lourdes;Guerrero-Velazquez, Celia
    • 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.

Expression of IL-17 Homologs and Their Receptors in the Synovial Cells of Rheumatoid Arthritis Patients

  • Hwang, Sue-Yun;Kim, Ho-Youn
    • Molecules and Cells
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    • v.19 no.2
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    • pp.180-184
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    • 2005
  • IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients. We also tested for induction of the IL-17 receptor homologs upon stimulation of the fibroblast-like synoviocytes (FLSs) of RA patients with IL-17. The patients' SFMCs expressed IL-17C, E and F in addition to IL-17A. As in the case of IL-17, IL-15 appears to be the major inducer of these homologs in RA SFMCs. We detected transcripts of IL-17R, as well as those of IL-17RB, C and D, in the FLSs of RA patients. Whereas IL-17R expression increased upon in vitro stimulation with IL-17, expression of IL-17RB, C and D was unchanged. However the possibility of cross-interaction between other IL-17 homologs and receptor isoforms remains to be investigated. Our data suggest that these additional homologs should also be considered as targets for immune modulation in the treatment of RA joint inflammation.

Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells

  • Lee, Kyoung-Hee;Lee, Chang-Hoon;Woo, Jisu;Jeong, Jiyeong;Jang, An-Hee;Yoo, Chul-Gyu
    • Molecules and Cells
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    • v.41 no.4
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    • pp.282-289
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    • 2018
  • Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) via the PI3K/Akt pathway. Blockade of $GSK-3{\beta}$ inactivation by overexpression of constitutively active $GSK-3{\beta}$ (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of $GSK-3{\beta}$ via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

Insulin Resistance and Serum Levels of Interleukin-17 and Interleukin-18 in Normal Pregnancy

  • Jahromi, Abdolreza Sotoodeh;Shojaei, Mohammad;Ghobadifar, Mohamed Amin
    • IMMUNE NETWORK
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    • v.14 no.3
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    • pp.149-155
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    • 2014
  • We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (p<0.05). Serum IL-18 level was significantly lower in subjects with first, second, and third trimesters of pregnancy in compared to non pregnant women (p<0.05). No significant correlations were found between serum IL-17 and IL-18 levels with insulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

Studies of Xanthium strumarium Extract Suppressing Th17-cell Differentiation and Anti-dermatitic Effect in BMAC-induced Atopy Dermatitis of NC/Nga Mice (창이자 추출물이 아토피 피부염 유발 생쥐의 비장 세포 Th17의 세포분화 억제에 따른 아토피 피부 상태에 미치는 영향)

  • Kim, Kum-Lan;Choe, Tae-Boo
    • KSBB Journal
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    • v.24 no.4
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    • pp.383-392
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    • 2009
  • Xanthii fructus which is well known as "Chang-ihjah" in Korea is the dried fruit of Xanthium strumarium L. (or Xanthium sibiricum PATR. Ex WIDD., Asteraceae. XS). Water extract of this fruit has been used for treatment of various inflammatory diseases such as tympanitis, allergic rhinitis, or ozena as alternative therapy material usually by oral administration in far Eastern countries including Korea. In this study, the effect of XS extract (XS-E) or XS-30% acetone fraction layer (XS-30% AFL) on the differentiation of $CD4^+$ T cells isolated from NC/Nga mouse and the production of IL-17 was investigated. The experimental results showed that $100\;{\mu}g$/mL of XS-E could decrease the production of IL-17 by $CD4^+$ Th17 cells by 2 fold and only $20\;{\mu}g$/mL of XS-30% AFL could inhibit 3.5 fold. The amount of IL-17A and IL-22 mRNA determined by real-time PCR was decreased remarkably when XS-E or XS-30% AFL was treated on $CD4^+$ Th17 cells(p<0.01, p<0.001). The amount of IL-17A protein determined by ELISA was also decreased remarkably(p<0.05, p<0.001). To study the effect of XS-E or XS-30% AFL on the proliferation of Th17 cells, $CD4^+$ T cells of a NC/Nga mouse was firstly differentiated by rIL-6/TGF-$\beta$ and then stimulated by rIL-23. The control group of Th17 cells were doubled every each day, while those of XS-E or XS-30% AFL treated group were shown to be delayed remarkably by these extracts. In conclusion, XS can inhibit the differentiation of Th17 cells of NC/Nga mouse and the production of IL-17 successfully, which may be a beneficial result for the treatment of atopic skin dermatitis.

Association of miR-1266 with Recurrence/Metastasis Potential in Estrogen Receptor Positive Breast Cancer Patients

  • Sevinc, Elif Demirdogen;Egeli, Unal;Cecener, Gulsah;Tezcan, Gulcin;Tunca, Berrin;Gokgoz, Sehsuvar;Tasdelen, Ismet;Tolunay, Sahsine;Evrensel, Turkkan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.291-297
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    • 2015
  • The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3' UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3' UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT-PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3' UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.

Antitumor Effect Of Bismuth-conjugated Anti-IL-2R Monoclonal Antibody(2E4) on a IL-2 Receptor Positive Tumor EL4J3.4

  • Kim, Sung-Hoon;Robert-W. Kozak;Chung, Kyeong-Soo;Ahn, Byung-Zun
    • Archives of Pharmacal Research
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    • v.17 no.3
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    • pp.194-198
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    • 1994
  • The antitumor effects of the 2E4 and anti--Tac, monoclonal antibodies directed to Il-2 receptor (IL-2R) conjugated with .alpha.-particle emitting radionuclide bismuth-212., were compared. The $^{212}Bi-2E4$ demonstratedspecific cytotocicity to EL4J3, 4, a I$L-2R^+$ cell line, than to EL4J, a $IL-2R^-$ cell line in thymidine incorporation assy. TEX>$^{212}Bi-2E4$ exerted the maximal antitumor effect in that % T/C in C57BL/6 mice implanted with EL4J3.4 ascitic tumor was 331% at the concentration of $50{\;}{\mu}Ci$, while that of $^{212}Bi-anti-Tac$ was 258% at $100{\;}{\mu}Ci$.

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Age-Associated Increasing of MCP-1 in Adults

  • Im, Jee-Aee;Kim, Sang-Hwan
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.183-187
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    • 2007
  • Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) playa key role in development of atherosclerosis. To take into account the atherogenic properties of MCP-1 and IL-8 and its influence on insulin resistance, we examined circulating levels of MCP-1 and IL-8 in adults. We recruited 292 subjects (84 males and 208 females) aged between 29 and 79 years. MCP-1 and IL-8 levels were measured by enzyme-linked immunosorbent assay. Age, total cholesterol, HDL-cholesterol, and LDL-cholesterol levels were significantly higher in female subjects (P<0.01, respectively), but diastolic blood pressure (BP) was significantly lower in female subjects compared to male subjects. MCP-1 and IL-8 levels were tended to increase with age, the highest in their seventies. MCP-1 (P=0.05) and IL-8 (P<0.01) levels were higher in males than in females. MCP-1 was positively correlated with age (r=0.17, P<0.05), IL-8 (r=0.26, P<0.01), fasting insulin (r=0.30, P<0.01), and HOMA-IR (r=0.29, P<0.01). In linear regression analysis, age was found to be independent factor associated with MCP-1 adjusted by age, BMI, fasting glucose, triglyceride, and systolic BP. In conclusion, age was found to be independent factor associated with MCP-1. It is possible that an increase of MCP-1 in adults with age may be risk to atherosclerosis and diabetic properties.

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Improvement of Bronchial Immune Hypersensitivity Reaction by Extracts from Chrysanthemum morifolium and Scutellaria baicalensis

  • Kyoung won Cho;Sung Sun Park;Hak Joo Choi
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.08a
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    • pp.78-78
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    • 2020
  • This study aimed to discover functional materials derived from resources, which can improve the troublesome symptoms of a bronchus by improving bronchial hyperresponsiveness as air pollution in Korea caused by fine dust and yellow dust is getting worse. Of natural resources grown naturally in Korea, Chrysanthemum morifolium(CM), and Scutellaria baicalensis(SB) have been used as a safe raw material for drinking or medicine for a long time, and it has been found that a combination of CS73 can improve bronchial health function in experimental animal models. Analysis of serum of animal models with asthma induced by ovalbumin (chicken egg albumin) and analysis of cytokine production in BALF (Bronchoalveolar lavage fluid) showed that inflammatory indices IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E were significantly reduced and that respective production of IL-2 and IFN-γ was significantly increased in the group taking extracts from CS73 when compared with the control group. These results suggested that the combination of CS73 could be used as a natural treatment for asthma. In addition, in the animal models that the combination of CS73 significantly decreased the respective production of IgE, histamine and TSLP when compared with the control group. In experimental models, the ratio of Chrysanthemum morifolium to Scutellaria baicalensis of 7 : 3 had more excellent effect than other combined experimental groups, which suggests that the above combination can be developed as a natural treatment for asthma and is valuable as a pharmaceutical composition with an effect of improving bronchial health, capable of contributing to the public health threatened by fine dust.

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Respiratory Protective Effect of Salvia plebeia R. Br. Extracts against Ambient Particulate Matter-induced Airway Inflammation (미세먼지 유도 기도염증에 대한 배암차즈기 추출물의 호흡기 보호 효과)

  • Song, Hyeongwoo;Ji, Kon Young;Kim, Bok Kyu;Yang, Won Kyung;Han, Chang Kyun;Shin, Han Jae;Park, Yang Chun;Hwang, Ji Sook;Kang, Hyung Sik;Kim, Seung Hyung
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.5
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    • pp.269-281
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    • 2017
  • Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.