• Journal of Acupuncture Research
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• v.21 no.2
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• pp.21-29
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• 2004

목적 : 본 연구는 Interleukin 4 Receptor (IL-4R) 유전자 다형성이 중풍의 발병과 관련이 있는지 알아보기 위해 수행되었다. 대상: 대구한의대학교부속 한방병원에 입원한 중풍환자 56명과 종합건진센터에 내원한 중풍 기왕력이 없는 건강인 83명을 대상으로 하였다. 방법 : 각 그룹에서 개개인마다 DNA를 분리 정제한 후 Taq polymerase로 증폭하여 한천 겔에서 전기영동을 하여 PCR 산물을 확인하였다. PCR 산물은 Pyrosequencing 과정을 통하여 IL4R의 유전형이 자동으로 판정되었다. 결과 : A/A, A/G, G/G의 세가지 유전자형이 검출되었으며 중풍군과 대조군 사이에 유의성 있는 차이가 발견되었다(p=0.005). 그러나 개별 allele 빈도에 있어서는 중풍군과 건강인 사이에 통계적인 유의성이 나타나지 않았다(p=0.995). 결론 : 이상의 결과를 통하여 IL4R 유전자 다형성은 중풍의 발병과는 관련성이 있는 것으로 사려되지만 더 많은 환자를 대상으로 다른 환경요인 또는 유전자와의 연관성에 대한 심도있는 연구가 필요하다고 하겠다.

• IMMUNE NETWORK
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• v.24 no.3
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• pp.21.1-21.16
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• 2024

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1β is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

• Microbiology and Biotechnology Letters
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• v.21 no.2
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• pp.144-149
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• 1993

We have identified a T cell-activating material in the culture supernatant of Streptomyces species. The factor in microbial culture supernatant (MCS) induced thymocyte proliferation in a does dependent fashion and it could be detected by immunoblot analysis using anti-interleukin-1(IL-1) antibody. The factor in MCS was slightly larger(about 21 kd) in its molecular weight than IL-1 on SDS-PAGE. When 125I-MCS was covalently coupled with homo-bifunctional cross-linking agent, disuccinimidyl-propionate to IL-1 receptor(IL-1R) on mouse thymoma cell(EL-4) and immunoprecipitated with anti-IL-1R antibody the molecular weight of this complex of 110 kd was observed.

• BMB Reports
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• v.48 no.12
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• pp.696-701
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• 2015

Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA. It stimulates pro-inflammatory cytokine and interferon production. Here we reported the expression of a novel isoform of TLR3 in human astrocyte cell lines whose message is generated by alternative splicing. The isoform represents the N-terminus of the protein. It lacks many of the leucine-rich repeat domains, the transmembrane domain, and the intracellular Toll/interleukin-1 receptor domain of TLR3. Type I interferons (interferon-α and interferon-β) induced the expression of this isoform. Exogenous overexpression of this isoform inhibited interferon regulatory factor 3, signal transducers and activators of transcription 1, and Inhibitor of kappa B α signaling following stimulation. This isoform of TLR3 also inhibited the production of chemokine interferon-γ-inducible protein 10. Our study clearly demonstrated that the expression of this isoform of TLR3 was a negative regulator of signaling pathways and that it was inducible by type I interferons. We also found that this isoform could modulate inflammation in the brain.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.531-546
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• 2017

Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor alpha ($TNF-{\alpha}$) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including 'chemotaxis', 'hematopoietic organ development', 'positive regulation of cell proliferation', and 'regulation of cytokine biosynthetic process'. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

• Journal of Life Science
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• v.21 no.1
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• pp.36-43
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• 2011

Diabetes mellitus is associated with vascular complications. Diabetic patients exhibit high levels of glycated adducts in serum compared to non-diabetic individuals. The aim of this study was to investigate whether extracellular glycated albumin (GA) predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells (AoSMCs) to GA not only enhanced interleukin-6 (IL-6) release but also activated promoter activity of the IL-6 gene. GA-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-2 and TIR-domain-containing adapter-inducing interferon-$\beta$ (TRIF). Extracellular signal-regulated kinase (ERK) inhibition and diphenyleneiodium (DPI) also attenuated IL-6 induction by GA. Mutation at the nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-binding site in the IL-6 promoter region suppressed promoter activation in response to GA. The present study proposes that GA would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4, EKR, and NF-${\kappa}B$ play active roles in the process.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.115-121
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• 2018

Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.65-74
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• 2017

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta ($IL-1{\beta}$) ($1ng/10{\mu}L$) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A ($GABA_A$) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the $IL-1{\beta}$-induced mechanical allodynia. In the control group, application of GABA ($100{\mu}M$) or muscimol ($3{\mu}M$) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the $IL-1{\beta}$-treated rats. These results suggest that some large myelinated $A{\beta}$ fibers gain access to the nociceptive system and elicit pain sensation via $GABA_A$ receptors under inflammatory pain conditions.

• Journal of Cancer Prevention
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• v.21 no.2
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• pp.95-103
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• 2016

Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in $Apc^{Min/+}$ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

• Journal of Periodontal and Implant Science
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• v.41 no.3
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• pp.149-156
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• 2011

Purpose: Globular adiponectin (gAd) is a type of adipocytokine, which is mainly produced by adipose tissue. It has been reported that gAd acts as a pro- as well as an anti-inflammatory factor. Interleukin (IL)-6 and IL-8 are pro-inflammatory cytokines. To investigate the role of gAd on periodontal tissues, the expression of adiponectin receptor 1 (AdipoR1) and the effect of gAd on the expression of IL-6 and IL-8 were investigated in periodontal ligament (PDL) and gingival fibroblasts. Methods: PDL and gingival fibroblasts were cultured from human periodontal tissues. gAd derived from Escherichia coli and murine myeloma cells were used. The expression of AdipoR1 was estimated by reverse transcription-polymerase chain reaction and western blot The expression of cytokines was measured by enzyme-linked immunosorbent assay. Results: PDL and gingival fibroblasts expressed both mRNA and protein of AdipoR1. gAd derived from E. coli increased the production of IL-6 and IL-8, but polymyxin B, an inhibitor of lipopolysaccharide (LPS), inhibited IL-6 and IL-8 production induced by gAd in both types of cells. gAd derived from murine myeloma cells did not induce IL-6 and IL-8 production in those cells. gAd derived from E. coli contained higher levels of LPS than gAd derived from murine myeloma cells. LPS increased production of IL-6 and IL-8 in PDL and gingival fibroblasts, but pretreatment of cells with gAd derived from murine myeloma cells did not inhibit LPS-induced IL-6 and IL-8 expression. Conclusions: Our results suggest that PDL and gingival fibroblasts express AdipoR1 and that gAd does not act as a modulator of IL-6 and IL-8 expression in PDL and gingival fibroblasts.