• 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.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.24.1-24.13
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• 2021

Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.

• Microbiology and Biotechnology Letters
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• v.16 no.4
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• pp.327-333
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• 1988

For optimal production of recombinant human interleukin-2 (IL-2) in E. coli the effect of fermentation conditions on cell growth, IL-2 production, and stability of recombinant cells were investigated. Among the complex nutrients tested in this work, yeast extract, peptone and corn steep liquor were found to be effective for recombinant cell growth. The recombinant cells were maintained stably under repression condition (3$0^{\circ}C$), but the stability of recombinant cells were drastically reduced upon induction of IL-2 expression (42$^{\circ}C$) even under the selection pressure. Addition of antibiotics to the culture medium resulted in the cell growth inhibition without significant improvement in recombinant stability. When the expression of IL-2 gene was induced at different growth phases, highest IL-2 production was achieved by the induction of IL-2 at the middle-exponential growth phase. It was found that the production of IL-2 significantly inhibited the cell growth and the ex-pression of other genes in the plasmid.

• Genomics & Informatics
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• v.14 no.4
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• pp.205-210
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• 2016

Interleukin-10 (IL10) plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL). Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients treated at the National Cancer Center, Korea. The median age was 57 years, and 70 patients (62.5%) were men. Clinical characteristics, including age, performance status, stage, and extra-nodal involvement, as well as cell lineage and International Prognostic Index (IPI), were evaluated. A total of four polymorphisms in IL10 with heterozygous alleles were analyzed for hazard ratios of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards regression analysis. Diffuse large B-cell lymphoma was the most common histologic type (n = 83), followed by T-cell lymphoma (n = 18), mantle cell lymphoma (n = 6), and others (n = 5). Cell lineage, IPI, and extra-nodal involvement were predictors of prognosis. In the additive genetic model results for each IL10 polymorphism, the rs1800871 and rs1800872 polymorphisms represented a marginal association with OS (p = 0.09 and p = 0.06) and PFS (p = 0.05 and p = 0.08) in B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These findings suggest that IL10 polymorphisms might be prognostic indicators for patients with B-cell NHL treated with R-CHOP.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.44-50
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• 2009

This study was conducted to evaluate the inflammation mechanisms of tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-4 (IL-4), and IL-$1{\beta}$-induced stimulation of A549 human epithelial cells. In the present study, A549 cells were stimulated with TNF-$\alpha$, IL-4 and IL-$1{\beta}$ to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. The effects of TNF-$\alpha$, IL-4 and IL-$1{\beta}$ on gene expression profiles in A549 cells were evaluated by oligonucleotide microarray and Real time RT-PCR. The gene expression profiles for the A549 cells varied depending on the cytokines. Also, the results of the microarray and Real time RT-PCR revealed that inflammatory-related genes were up-regulated in cytokine stimulated A549 cells. Cytokines can affect inflammation in A549 cells. A microarray-based genomic survey is a high-throughput approach that enables evaluation of gene expression in cytokine stimulated cell lines.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.421-431
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• 2016

Recently, poly-γ-glutamic acid synthetase A (pgsA) has been applied to display exogenous proteins on the surface of Lactobacillus casei or Lactococcus lactis, which results in a surface-displayed component of bacteria. However, the ability of carrying genes encoded by plasmids and the expression efficiency of recombinant bacteria can be somewhat affected by the longer gene length of pgsA (1,143 bp); therefore, a truncated gene, pgsA, was generated based on the characteristics of pgsA by computational analysis. Using murine IL-10 as an exogenous gene, recombinant Lactobacillus plantarum was constructed and the capacity of the surface-displayed protein and functional differences between exogenous proteins expressed by these strains were evaluated. Surface expression of IL-10 on both recombinant bacteria with anchorins and the higher expression levels in L. plantarum-pgsA'-IL-10 were confirmed by western blot assay. Most importantly, up-regulation of IL-1β, IL-6, TNF-α, IFN-γ, and the nuclear transcription factor NF-κB p65 in RAW264.7 cells after stimulation with Poly(I:C) or LPS was exacerbated after co-culture with L. plantarum-pgsA. By contrast, IL-10 expressed by these recombinant strains could reduce these factors, and the expression of these factors was associated with recombinant strains that expressed anchorin (especially in L. plantarum-pgsA'-IL-10) and was significantly lower compared with the anchorin-free strains. These findings indicated that exogenous proteins could be successfully displayed on the surface of L. plantarum by pgsA or pgsA', and the expression of recombinant bacteria with pgsA' was superior compared with bacteria with pgsA.

• The Journal of Internal Korean Medicine
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• v.45 no.3
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• pp.508-518
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• 2024

Objectives: To report a correlation of IL-6 of pancreatic cancer and cancer progression in three pancreatic cancer patients. Method: Three pancreatic cancer patients were monitored for changes in IL-6 levels, tumor markers (CEA, CA19-9), and clinical outcomes over their treatment period. Results: Patient 1's IL-6 levels rose with liver metastasis and tumor progression, coinciding with increases in tumor markers. Patient 2's IL-6 levels remained elevated during chemotherapy, correlating with tumor growth. Patient 3's IL-6 levels spiked prior to cancer progression. Conclusion: Elevated IL-6 levels were observed in advancing pancreatic cancer patients, suggesting IL-6 as a potential biomarker for monitoring cancer progression in pancreatic cancer. Regular IL-6 monitoring could improve prognostic evaluations and treatment strategies.

• Genomics & Informatics
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• v.9 no.3
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• pp.114-120
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• 2011

Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide poly-morphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4 -IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=$1.65{\times}10^{－4}$ in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.

• Proceedings of the Korean Magnestics Society Conference
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• 2009.12a
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• pp.186-186
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• 2009

• Bulletin of the Korean Chemical Society
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• v.31 no.4
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• pp.921-924
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• 2010

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.