• 동의생리병리학회지
• /
• 제17권6호
• /
• pp.1479-1486
• /
• 2003

In order to evaluate the antiallergic effects of Kamiohihyosan(KCHS), studies were done. We measured the cytotoxic activity for lung fibroblast cell, cytokines transcript expression, production of IL-4, IL-10, IFN-γ, proliferation of B cell in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells. The results were obtained as follows: KCHS was not showed cytotoxicity in the fibroblast lung cell, KCHS increased the gene synthesis of INF-γ, TNF-α, IL1-β, IL-6, IL-10(m-RNA), KCHS decreased the gene synthesis of IL-4, IL-5, TGF-β(m-RNA), KCHS decreased the appearance of IL-4, IgE significantly, KCHS increased the appearance of IL-10, IFN-γ significantly, KCHS decreased the proliferation of B cell significantly, The facts above prove that KCHS is effective against the allergy. Thus, I think that we should study on this continuously.

• Genomics & Informatics
• /
• 제3권4호
• /
• pp.149-153
• /
• 2005

Asthma is an inflammatory airways disease characterized by bronchial hyperresponsiveness and airways obstruction, which results from a complex interaction of genetic and environmental factors. Interleukin (IL)-13 and IL-4 are important in IgE synthesis and allergic inflammation, therefore genes encoding IL-13 and IL-4 are candidates for predisposition to asthma. In the present study, we screened single-nucleotide polymorphisms (SNPs) in IL-13 and IL-4 and examined whether they are risk factors for asthma. We resequenced all exons and the promoter region in 12 asthma patients and 12 normal controls, and identified 18 SNPs including 2 novel SNPs. The linkage disequilibrium(LD) pattern was evaluated with 16 common SNPs, and haplotypes were also estimated within the block. Although IL-13 and IL-4 are localized within 27 kb on chromosome 5q31 and share many biological profiles, this region was partitioned into 2 blocks. One SNP and three SNPs were determined as haplotype-taggingSNPs (htSNPs) within IL-13 and IL-4 haplotype-block, respectively. No significant associations were observed between any of the SNPs or haplotypes and development of asthma in small number of Korean subjects. However, the genetic variants of IL-13 and IL-4 would provide valuable strategies for the genotyping studies in large population.

• 대한한방소아과학회지
• /
• 제30권3호
• /
• pp.1-30
• /
• 2016

Objectives Previous studies have found out that Forsythiae Fructus (FF) extracts have anti-atopic activities by in vitro experiment. In order to understand more about FF extracts' benefit, we subdivided FF extracts depending on systematic fractionation method by using Methylene chloride (MC), Ethyl acetate (EtOAc), n-BuOH and n-hexane (n-Hx). This study is designed to examine the effect of FF fractions on the PMA- ionomycin-induced activation of RBL-2H3 mast cell lines in vitro and on the DNCB-induced activation of NC/Nga mice in vivo. Methods For this study, we examined IL-4, IL-13 production by ELISA analysis, IL-4, IL-13, IL-31, IL-31RA and TNF-${\alpha}$ mRNA expression by real-time PCR and manifestations of AP-1 and MAPKs transcription factors by western blotting in vitro. Through in vitro experiment, we selected FF n-BuOH fraction that seems the best effective in atopic dermatitis then induced it on NC/Nga mice by DNCB. We measured mice's WBC, eosinophil and neutrophil in heart blood, IL-4, IL-5, IFN-${\gamma}$ in the spleenocyte culture supernatant, the absolute cell numbers of CD4+, CD8+, B220+CD23+, CD3+CD69+ and Gr-1+CD11b+ in the PBMCs, ALN and dorsal skin, IL-5, IL-13, IL-31, IL-31RA in the dorsal skin by real-time PCR and the distribution of immune cells by H&E on dorsal skin and ANL and toluidine blue staining on dorsal skin. Results FF n-BuOH fraction suppressed IL-4, IL-13 production and mRNA expression of IL-4, IL-13, IL-31, IL-31RA and TNF-${\alpha}$. Results from the western blot analysis showed that FF n-BuOH fraction reduced the activation of the mast cell specific transduction factors involved in AP-1 by suppressing JNK and ERK phosphorylation. In the gross, atopic dermatitis induced by DNCB in NC/Nga mice were improved by oral administration of FF n-BuOH fraction. Oral FF n-BuOH fraction also decreased the level of IgE in mice's serum and the level of IL-4 and IL-5 in the spleenocyte culture supernatant, cell numbers of CD8+, B220+CD23+ in the PBMCs, CD4+ in the ALN and CD4+, Gr-1+CD11b+ in the dorsal skin and suppressed mRNA expression of IL-5, IL-13, IL-31, IL-31RA in the dorsal skin. Histological examination showed that infiltration levels of immune cells in atopic dermatitis induced NC/Nga mice were improved by FF n-BuOH fraction. Conclusions FF n-BuOH fraction can reduce pruritus by suppressing IL-31, IL-31RA secretion and modulate molecular mediators and immune cells associated with atopic dermatitis induced in NC/Nga mice which may have played a significant role in recovering atopic dermatitis symptoms.

• 대한한방소아과학회지
• /
• 제30권4호
• /
• pp.29-59
• /
• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• 대한한의학회지
• /
• 제25권2호
• /
• pp.207-219
• /
• 2004

Objectives : We investigated to find the relationship between single-nucleotide polymorphism (SNP) of IL4R, IL-10 and bee venom therapy efficacy in patients with RA treated with bee venom for 8 weeks. Methods : Korean RA patients (n=114) and healthy subjects (n=109) were included in this prospective study. Korean bee venom was dissolved in saline (diluted 1:3000) and administrated into acupuncture points. Bee venom therapy was applied twice a week and continued for 8 weeks. The clinical response was evaluated using various assessments before and after treatment. Disease severity was measured by determining the number of tender joints and swollen joints. Laboratory studies included ESR, CRP, and rheumatoid factor. Genotyping for IL-4R and IL-10 polymorphism was done by pyrosequencing analysis. Results : 1. In IL4R genotypes, there was significant difference between RA ptitients tind controls group. 2. In IL4R genotypes, there was significant difference among Good, Mild and Bad responders to in RA patients, but in the frequency of alleles and carriers, there were no significant difference. 3. There was no significant difference between RA patients and controls group in IL-10 gene genotypes. 4. In IL-10 genotypes, there was no significant difference among Good, Mild and Bad responders to in RA patients. 5. There was no significant difference in the improvement of ESR, CRP and KHAQ scores after bee venom therapy in RA patients among the IL4R or IL-10 genotypes. Conclusions : In IL-4R genotypes, there was significant difference between RA patients and control group, and among Good, Mild and Bad responders in RA patients. However, in IL-10 genotypes, there was no significant difference between RA patients and controls group and among Good, Mild and Bad responders in RA patients.

• 대한한방소아과학회지
• /
• 제25권1호
• /
• pp.28-39
• /
• 2011

Objectives: SaengRyoSaMulTang is a herbal formula in Oriental Medicine, known anti-allergens. However, its mechanism and cellular targets have not been found yet. Thus the study has developed to investigate the suppressive effect of SaengRyoSaMulTang. Methods: In the study, cellular viability, IL-4, IL-13 mRNA expression, IL-4, IL-13 production, manifestations of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}$B p65 transcription factors were examined by Real-Time PCR, ELISA analysis and western blotting. Results: As a result of treating with SaengRyoSaMulTang extract(SRSMT), the study has shown that the amount of Th2 cytokines, which include PI induced IL-4 and IL-13, plays a significant role in suppressing effect. RBL-2H3 mast cells significantly suppressed the PI-induced Th2 cytokine production including IL-4 and IL-13 in a dose dependent manner. PI-induced IL-4 and IL-13 production was significantly suppressed by SRSMT intervention. Western blot analysis of transcription factors involving IL-4 and IL-13 expression also revealed a prominent decreases of mast cell's specific transcription factors including GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos, but NF-${\kappa}$B p65. Conclusions: The study suggests that the anti-allergenic activities of SRSMT may regulate the transcription factors GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos inhibiting Th2 cytokines IL-4 and IL-13 in mast cells.

• Journal of Periodontal and Implant Science
• /
• 제50권2호
• /
• pp.74-82
• /
• 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.

• 생명과학회지
• /
• 제16권5호
• /
• pp.780-787
• /
• 2006

본 연구진은 일차로 BALB/C 마우스를 이용하여 항원으로 ovalbumin을 사용하여 천식을 유발하여 폐 내 세포구성에 미치는 영향을 다른 실험방법에 의해 만들어진 천식모델과 비교하여 살펴보았고 이차로 천식 발생에 중요한 역할을 하는 것으로 알려진 IL-4와 IL-10 knock out (KO) 마우스를 이용하여 천식모델을 구축하여 천식인자를 가진 개체에서의 반응과 천식관련인자가 결핍된 개체에서의 반응성의 차이를 살펴보았다. 천식의 유발은 실험 1일째 $20\;{\mu}g$ ovalbumin으로 감작시킨 후 실험 14일에 재감작을 시켰다. 그 후 nebulizer를 이용하여 nasal inhalation을 28일, 29일, 30일에 실시하여 천식을 유발시켰다. 천식 유발의 확인은 기관지폐포 세척술로 채취한 폐 내 세포액을 이용하여 총 세포수 및 염증세포의 증가와 폐 내 세포와 폐조직의 염색을 통해 분포율을 확인하였다. 천식의 발병 과정에서 IgE 관련 과민반응을 주도하는 IL-4와 Th2 세포의 기능을 억제한다고 알려진 IL-10의 면역화학염색을 통해 그 발현정도를 관찰하였다. BALB/c 마우스의 천식유발군의 경우 천식의 특징인 염증세포의 증가와 호산구의 증가와 세기관지 주위 염증세포의 침윤 및 기도 상피의 비후를 관찰할 수 있었다. 따라서 본 실험에 응용된 천식유발 방법은 적합하였으며 천식유발 절차가 성공적으로 수행되었음을 확인하였다. IL-4 및 IL-10 KO 마우스를 이용한 천식유발군의 경우 BALB/c 마우스를 이용한 천식유발군보다 호산구의 증가 정도가 미약하게 관찰되었고, 폐조직 내 염증세포의 침윤 정도도 감소하였다. 천식매개인자인 IL-4와 IL-10의 면역조직화학염색 결과에서도 양성반응이 거의 나타나지 않았다. 본 연구 결과, IL-10이 IL-4와 같이 천식과 관련하여 세기관지 염증 반응을 증가시키는 역할을 하는 것으로 생각된다.

• 약학회지
• /
• 제56권5호
• /
• pp.326-332
• /
• 2012

Mast cells play pivotal pathologic roles in allergic disease involving T helper 2 (Th2) cytokine such as interleukin (IL)-4 and IL-13. Fisetin has been known as an anti-allergic agent having inhibitory effects on the IL-4 and IL-13 gene expressions in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on IL-4 and IL-13 in activated mast cells have been incompletely elucidated. In this study we found that fisetin significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-induced production of IL-4 and IL-13 in mast cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppression of c-Fos was prominent together with significant down-regulation of nuclear factor of activated T-cell (NF-AT) and NF-${\kappa}B$, but not c-Jun. Furthermore, the nuclear expression of GATA binding protein 2 (GATA-2) transcription factor was significantly down-regulated by fisetin. Taken together, our study indicated fisetin has suppressive effects on IL-4 and IL-13 gene expression through the regulation of selective transcription factors.

• 대한한방내과학회지
• /
• 제22권3호
• /
• pp.367-377
• /
• 2001

Objectives: We aimed to identify. the effect of Jeongcheon-tang(定喘湯) and Cheongsangboha-tang(淸上補下湯) on the transcriptional activities of cytokine IL-4, IL-5, IL-6 and IL-10 involved in asthma model. Materials and Methods: RBL-2H3 cell lines were used. Cells were stimulated with calcium inophore($2{\mu}M$ : Sample group 1, $4{\mu}M$ : Sample group 2) for maximal gene expression. After 3rd treatment of samples and incubation(per 24hours), total cellular RNAs were collected using Trizol solution method. Then transcriptional activities of IL-4, IL-5, IL-6 and IL-10 were measured by RT-PCR with electrophoresis. Results: In IL-4 study, Jeongcheon-tang treated group showed 82.76%(Sample group 1) of transcriptional activities compared to the control group and Cheongsangboha-tang treated groups showed 85.77% (Sample group 1), 89.42% (Sample group 2) of transcriptional activities compared to the control groups. In IL-5 study, Jeongcheon-tang treated groups showed 88.24%(Sample group 1), 98.83%(Sample group 2) of transcriptional activities compared to the control groups and Cheongsangboha-tang treated group showed 73.66%(Sample group 2) of transcriptional activities compared to the control group. In IL-6 study, Jeongcheon-tang treated group showed 92.95%(Sample group 2) of transcriptional activities compared to the control group and Cheongsangboha-tang treated group showed n.40%(Sample group 2) of transcriptional activities compared to the control group. In IL-10 study, Jeongcheon-tang treated group showed 118.46% (Sample group 2) of transcriptional activities compared to the control group. Conclusions: This study shows that Jeongcheon-tang has the inhibitory effect on the transcription of IL-4, IL-5, IL-6 gene expression and the increasing effect on the transcription of IL-10 gene expression, and Cheongsangboha-tang has the inhibitory effect on the transcription of IL4, IL-5 and IL-6 gene expression in RBL-2H3 cell lines. Advanced studies are required to investigate the mechanisms of inhibition or increase by herbal medicine in asthma model.