• Clinical and Experimental Pediatrics
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• v.51 no.7
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• pp.754-759
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• 2008

Purpose : Abnormal activation patterns of Th1/Th2-cells have been suggested to increase the prevalence of allergic diseases. Prevention is regarded as an important corner stone in the management of allergic diseases. In this study, we have investigated the relationship between cord blood levels of IL-4, IL-10, and IL-12 in preterm newborns and the development of allergic respiratory diseases in infancy Methods : Forty-six preterm newborns born at the Ewha Womans University Mokdong Hospital between January 2003 and July 2005, were enrolled for this study, and consent was obtained to test their cord blood samples. Clinical history was obtained from the hospital records. Cord blood was obtained at birth and kept frozen until it was tested. The levels of IL-4, IL-10, and IL-12 were determined by enzyme-linked immunosorbent assay (ELISA). Results : All infants were followed-up for a median of $16.0months{\pm}13.2d$ (range, 12.0 to 36.0 months). Eighteen infants who developed wheezing showed lower cord blood levels of IL-12 ($366.60{\pm}140.40$ vs $435.09{\pm}91.20pg/mL$, P=0.009). Cord blood levels of IL-4 and IL-10 showed no significant difference between the two groups. Four newborns who later developed asthma, and infants with asthma showed lower IL-12 level in the cord blood than other groups. Conclusion : Lower concentration of cord blood levels of IL-12 in newborns who later developed wheezing and asthma suggested that they had abnormal activation patterns of Th1/Th2-cells at the time of birth, and cord blood IL-12 level can be used as a predictor of allergic respiratory diseases.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• Development and Reproduction
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• v.23 no.3
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• pp.231-238
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• 2019

Interleukin-8 (IL-8) is an inflammatory cytokine that plays an important role in the inflammatory response through the activation of neutrophil cells. The expression of IL-8 was investigated in early developmental stages of the olive flounder and in tissues of 8-month-old individuals. The expression of IL-8 increased after the initiation of the immune system rather than at the early stage of development, and high expression was observed in the gills and spleen, the organs associated with immunity and metabolism. In addition, IL-8 expression after infection by viral hemorrhagic septicemia virus significantly increased in the fin, gill, muscles, and spleen. These results suggest that IL-8 is closely related to inflammation and immune regulation in the immune response of the olive flounder and may be used as a basis for studies on the immune systems of other fish.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.367-377
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• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.104-112
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• 2009

The purpose of this study was to investigate the anti-inflammatory effects of extract from GuBoEum(GBE) on the peritoneal macrophage. To evaluate anti-inflammatory effects of GBE. I measured cytokines (interleukin-6; IL-6, interleukin-12; IL-12, tumor necrosis factor-$\alpha$; TNF-$\alpha$) and nitric oxide (NO) production in lipopolysacchride (LPS)-induced macrophages. Furthermore, I examined molecular mechanism using western blot and also LPS-induced endotoxin shock. Extract from GBE does not have any cytotoxic effect in the peritoneal macrophages. Extract from GBE reduced LPS-induced IL-6, TNF-$\alpha$, IL-12 and NO production in peritoneal macrophages. GBE inhibited the activation of extracelluar signal-regulated kinase (ERK), C-Jun $NH_2$-terminal kinase (JNK) but not of p38, degradation of $I{\kappa}B-{\alpha}$ in the LPS-stimulated peritoneal macrophages. GBE inhibited the production of TNF-$\alpha$, IL-6 and IL-12 in serum after LPS injection. These results suggest that GBE may inhibit the production of TNF-$\alpha$, IL-6, and IL-12 through inhibition of ERK and JNK activation, and that GBE may be beneficial oriental medicine for inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• v.19 no.4
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• pp.424-430
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• 2009

IL-10 is an important anti-inflammatory cytokine that can inhibit the production of many pro-inflammatory cytokines. Both human and animal studies have shown that pro-inflammatory cytokines play an important role in pneumonia and other inflammatory lung diseases. In the present study, IL-10 knockout(KO) and wild-type mice were infected with Corynebacterium kutscheri to determine whether the severity of pathogenesis and whether protective immunity could be altered in the absence of IL-10. The survival rate was significantly lower in IL-10 KO mice than wild-type mice. The number of neutrophils in bronchoalveolar lavage fluid and blood were found to be higher in IL-10 KO mice than wild-type mice. IL-10 KO mice showed greater neutrophil infiltration, excessive inflammation, and weight-loss compared with wild-type mice. Furthermore, upregulation of IFN-$\gamma$ in bronchoalveolar lavage fluid, and upregulation of MIP-$1{\alpha}$ and IP-10 mRNA in the lungs of IL-10 KO mice compared with wild-type mice after C. kutscheri infection were observed. These results suggest that IL-10 plays an important role in the anti-inflammatory properties against C. kutscheri infection, and that lack of IL-10 leads to a more severe pulmonary inflammatory response. This increased susceptibility to C. kutscheri pneumonia is at least in part caused by IL-10 deficiency and severe recruitment of neutrophils.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Journal of Sasang Constitutional Medicine
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• v.24 no.1
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• pp.54-65
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• 2012

1. Objective : The purpose of this study is to investigate the effects of TAM (Taraxacum mongolicum) on Th2 cytokine production in MC/9 mast cells. 2. Methods : The effects of TAM was analyzed by ELISA and Real-time PCR in MC/9 mast cells. Levels of IL-5, IL-13 were measured using enzyme-linked immunosorbent assays(ELISA). mRNA levels of IL-4, IL-5, IL-6, IL-13 were analyzed with Real-time PCR. 3. Results : 1) TAM inhibited the IL-4 production significantly in comparison to PI-control group at concentration of $50{\mu}g/ml$, $100{\mu}g/ml$, $200{\mu}g/ml$. 2) TAM inhibited the IL-13 production significantly in comparison to PI-control group at concentration of $50{\mu}g/ml$, $100{\mu}g/ml$, $200{\mu}g/ml$. 3) TAM inhibited the IL-4 mRNA expression significantly in comparison to PI-control group at concentration of $100{\mu}g/ml$. 4) TAM inhibited the IL-5 mRNA expression significantly in comparison to PI-control group at concentration of $50{\mu}g/ml$, $100{\mu}g/ml$. 5) TAM inhibited the IL-6 mRNA expression significantly in comparison to PI-control group at concentration of $100{\mu}g/ml$. 6) TAM inhibited the IL-13 mRNA expression significantly in comparison to PI-control group at concentration of $100{\mu}g/ml$. 4. Conclusions : These results indicate that TAM (Taraxacum mongolicum) has the effect of decreasing the Th2 cytokine production in the MC/9 mast cell.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.106-113
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• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.635-644
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• 2019

Background: To increase the pharmacological effects of red ginseng (RG, the steamed root of Panax ginseng Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo. Methods: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-${\alpha}$, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer. Results: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice. Conclusion: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.