• Genomics & Informatics
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• v.4 no.3
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• pp.103-109
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• 2006

IL-28RA is one of the important candidate genes for complex trait of genetic diseases, but there are only a few published results for this gene. Previously, we identified eighteen SNPs and two variation sites in the entire coding regions of IL-28RA including promoter regions, and suggested that the g.32349G>A polymorphism of IL-28RA might be associated with susceptibility to allergic rhinitis. In this study, we chose seven SNPs (g.-1193A>C, g.-30C>T, g.17654C>T, g.27798A>G, g.31265C>T, g.31911C>T and g.32349G>A) of IL-28RA, and attempted to find out whether these polymorphisms were furtherassociated with genetic predisposition of asthma. We analyzed the genotype and allele frequencies of IL-28RA polymorph isms between the asthma patients and healthy controls. We also investigated the frequencies of haplotype constructed by these SNPs between asthma patients and controls. Our results suggest that the polymorphisms of IL-28RA gene were not associated with susceptibility to asthma, and not with IgE production and eosinophil recruitment. The haplotype frequencies by these SNPs also not significantly associated between the healthy controls and asthma patients. This result indicates that the IL -2BRA polymorphisms might be not associated withasthma susceptibility.

• Korean journal of dermatology
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• v.56 no.10
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• pp.609-613
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• 2018

Background: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. Objective: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). Methods: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. Results: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. Conclusion: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.310-319
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• 2003

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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• pp.471-480
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• 2020

Background: The roots of Cirsium japonicum var. ussuriense (RCJ) have been used as traditional medicine in Korea for hematuria and hematemesis. These extracts exert anti-oxidative and anti-inflammatory effects by scavenging for free radical and regulating the inflammatory response. However, the effect of RCJ on rheumatoid arthritis (RA) has not been elucidated. Thus, we evaluated the water extract of RCJ (WRCJ) using type II collagen-induced RA models. Methods and Results: RA was induced by immunization with type II collagen. All experimental materials were orally administered daily for three weeks. The positive control group was administered with 0.2 mg/kg methotrexate (n = 7), while the experimental group was administered with WRCJ (100 or 500 mg/kg, n = 7). Serum levels of TNF-alpha, Interleukin 6 (IL-6), and type II collagen IgG (CII) were measured using ELISA. Administration of 500 mg/kg WRCJ decreased the levels of TNF-alpha, IL-6, and CII. Moreover, WRCJ treatment diminished swelling of hind legs and infiltration of inflammatory cells in RA models' synovial membrane. Conclusions: These results indicate that WRCJ could improve RA, reduce inflammatory indicators and synovial inflammation. However, further experiments are required to determine how WRCJ can influence the signal transduction pathway in RA.

• Journal of Periodontal and Implant Science
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• v.48 no.6
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• pp.347-359
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• 2018

Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

• Journal of Acupuncture Research
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• v.25 no.4
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• pp.81-94
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• 2008

Rheumatoid arthritis(RA) is a general, chronic, inflammatory and auto-immune disease and it can lead to joint edema, pain, stiffness which are caused by an inflammation in synovium covering our joints. Ulmus davidiana Planchon is a traditional herb used for the treatment on various inflammations, gastrointestinal trouble, ENT(ear, nose, and throat) disease, edema, cancer etc. and it works effectively on arthritis as well. In these study to search for the treatment efficacy of Ulmus davidiana Planchon in RA, I measure manifestation of cytokine gene in synoviocyte treated with Ulmus davidiana Planchon herbal acupuncture and in EL-4 cell, manifestation of cytokine gene cell related to T-cell. And after Ulmus davidiana Planchon herbal acupuncture treatment in Collagen induced arthritis(CIA) which has been known by a general model of RA, DBA mice, I observed foot thickness, general shape of synovium, early cytokine induce CIA and, generation and mutation of cytokine related to the control of T-cell specialization. It comes to conclusion as belows. 1. In synovium treated with Ulmus davidiana Planchon herbal acupuncture, there was the decrease in MIF mRNA does-dependently. Incase of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in the damage in synovium and generation of the MIF which is related to induction of the early RA cytokine and IL-6 proinflammatory cytokine. 2. In case of EL-4 treated with Ulmus davidiana Planchon herbal acupuncture, there were decrease in the manifestation of the IL-2 mRNA, but the increase in the manifestation of the IL-4 does-dependently. 3. In the synovium of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in generation of IL-2, IL-12 and CD-28, but the increase in generation of IL-4. These result suggest that Ulmus davidiana Planchon can block the process of the early RA by Inhibiting MIF activation, and mitigate Rheumatoid Arthritis by controlling Tcell specialization.

• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.262-274
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• 2007

Objective : It has been reported that two-repeats ($IL1RN^{\ast}2$) of interleukin-1 receptor antagonist (IL-1Ra) gene is associated with ischemic stroke, and that Ala allele of the common Pro12Ala polymorphism in $PPAR-{\gamma}2$ isoform is associated with reduced risk for type 2 DM and its complications. The aim of the present study is to assess the association of IL-1Ra and $PPAR-{\gamma}2$ Pro12Ala polymorphism with the presence of ischemic stroke in the case of diabetic and non-diabetic patients. Methods : Genomic DNA was obtained from 373 healthy subjects, 157 DM subjects without ischemic stroke (known DM duration ${\ge}10$ years) and 302 ischemic stroke patients (including with DM). IL-1Ra polymorphism was analysed by polymerase chain reaction (PCR), and $PPAR-{\gamma}2$ polymorphism by restriction fragment length polymorphism after PCR. Results : $IL1RN^{\ast}1/IL1RN^{\ast}2$ genotype was associated with significantly increased risk for DM (OR=2.86, P = 0.0008) and ischemic stroke (OR=2.74, P = 0.0016). Pro/Ala genotype was associated with the reduced risk for DM (OR=0.53, P = 0.0491) and ischemic stroke (OR=0.38, P = 0.0039). They were also associated with the reduced risk for ischemic stroke in the DM patients compared with DM without ischemic stroke (OR=0.25, P = 0.0321). Conclusions : $IL1RN^{\ast}2$ allele could be an accelerating factor, not a predictive marker for ischemic stroke in type 2 DM. The Pro/Ala genotype of $PPAR-{\gamma}2$ Pro12Ala polymorphism may be associated with reduced risk for ischemic stroke with type 2 DM. Therefore it could be a useful predictive marker for ischemic stroke in Korean type 2 DM.

• Journal of Pharmacopuncture
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• v.10 no.3
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• pp.21-28
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• 2007

Aim This study was done to investigate whether SPP has inhibitory effects on the activation of RAW 264.7 cells. Method In tumor necrosis factor-a (TNF-a)/ interleukin-1b (IL-1b) and IL-6, the mRNA expression of molecular indicators related to inflammatory changes of the Reumatoid Arthritis (RA) were examined using quantitative real-time PCR. Results The treatment of SPP significantly suppressed the expression of proinflammatory cytokines and chemokines such as TNF-a, IL-1b, IL-6 compared with the control. The expression of NOS-II was considerably reduced, which was accompanied by a reduction in the production of nitric oxide (NO). It also reduced the expression of $TNF-{\alpha}$ in serum of Balb/c mice compared with control group. Conclusion SPP is an effective herbal material for suppressing the inflammation related cytokines of RAW 264.7 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1233-1242
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• 2007

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which might be mediated by the altered activation of Immune system, ultimately leading to the destruction of cartilage and bone. To examine effects of GHS on rheumatoid arthritis DBA/1J mice were immunized with bovine type II collagen to induced arthritis and then treated with GHS once a day for 7 weeks. Oral administration of GHS (200 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/Kg), a positive control. The severity of arthritis within the knee joints, which was evaluated by histological assessment of cartilage destruction and pannus formation, was also lowered by GHS. The production of TNF-and IL-6 in serum was significantly suppressed. The levels of IFN-g in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. The levels of IgG and IgM RA factor were also decreased in the serum. FACS analysis indicated that B cells (in DLN), CD3+ T cells (in spleen, and paw joint), CD11b+Gr-1+ cells (in paw joint), CD3+CD49b(DX5) (in PBMC) were decreased and there was increased proportion of CD3+, CD4+, CD8+, CD4+CD25+ T cells in DLN. In conclusion, our results demonstrates that GHS significantly suppressed the progression of CIA and this action was characterized by the decreased production of TNF-a, IL-6, and rheumatoid factors, and modulations of immune cell populations.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.248-254
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• 2003

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.