• Journal of dental hygiene science
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• v.23 no.4
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• pp.296-301
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• 2023

Background: Periodontal disease is a major cause of tooth loss in adults and is a representative oral disease commonly suffered by most people around the world. Mainly the proliferation of Gram-negative bacteria and secreted virulence factors cause an inflammatory response and destroy periodontal tissue. Gossypetin, isolated from Hibiscus sabdariffa L, is known to have various pharmacological effects, including antibacterial and anticancer activities. We aimed to confirm the anti-inflammatory effect of gossypetin through interleukin-6 (IL-6) regulation in human gingival fibroblasts (HGFs) stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a major cause of adult periodontitis. Methods: CCK-8 assay was performed to confirm the concentration-dependent cytotoxicity of gossypetin against HGFs. The secretion level and mRNA expression of IL-6, an inflammation-related cytokine, and the effect of gossypetin on these in HGFs stimulated with P. gingivalis LPS were confirmed by ELISA and qRT-PCR analysis, respectively. Results: Up to a concentration of 100 µM gossypetin with or without P. gingivalis LPS, the survival rate for HGFs was maintained at over 95% and showed no toxicity. ELISA and qRT-PCR analysis results showed that P. gingivalis LPS increased IL-6 secretion and mRNA levels in HGFs compared to the control group. However, this increase in IL-6 was significantly down-regulated by gossypetin treatment in a dose-dependent manner. In particular, 80 µM gossypetin inhibited IL-6 production to the level of the control group. Conclusion: These results indicated that gossypetin attenuated IL-6 production in HGFs stimulated by P. gingivalis LPS, which may ultimately suppress the inflammatory response in periodontal tissue. Therefore, gossypetin may have potential as a natural ingredient for the prevention and treatment of periodontal disease.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.407-419
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• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.89-89
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• 1997

Fangchinoline and Tetrandrine are the major alkaloids of bis-benzylisoquinoline structure isolated from Stephania tetrandra which has been used as anti-inflammatory drug. The purpose of this study was to investigate the inhibitory effects of Fangchinoline and Tetrandrine on cyclooxygenase, interleukin-5(IL-5) and interleukin-6 (IL-6) as anti-inflammatory mechanisms. Tetrandrine at 100 ${\mu}$M did not show any inhibitory effect but Fangchinoline showed 31% of inhibition on cyclooxygenase. In addition, in mIL-5-dependent Y16 proliferation assay, Tetrandrine at 30 ${\mu}$M exhibited more than 50% of inhibition but Fangchinoline did not any effect. However in hIL-6-dependent MH60 proliferation assay, more than 50% of inhibition was observed by both of Fangchincline and Tetrandrine at 30 ${\mu}$M. Fangchinoline and Tetrandrine also showed anti-inflammatory effects by croton oil induced mouse ear edema test.

• Journal of Microbiology and Biotechnology
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• v.33 no.7
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.109-114
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• 1996

We have previously reported that Korean schizophrenic patients hove low production of IL-2 in vitro suggestive of autoimmunity to the pathogenesis of the disorder. In an attempt to further explore this issue, we measured in vivo serum levels of interleukins(IL-$1{\beta}$, IL-2, and IL-6) using a quantitative "sandwich" enzyme immunoassay(ELISA) in 26 male schizophrenic patients and in 26 age-matched normal controls. Patients met DSM-IV criteria for schizophrenia and were drug free for at least six months. The severity of symptoms was assessed by SANS and SAPS. We found a significant increase of IL-2 level(p<0.05) in schizophrenic patients as compared with normal controls. There were significant positive correlations between IL-2, IL-6 levels and negative symptom scores. There were no correlations between age, age at onset, duration of illness and interleukin levels. Our results may support the hypothesis of viral-autoimmune dysfunction in schizophrenia. IL-2 or IL-6 may be associated with specific clinical feature in schizophrenic syndrome, especially negative symptom.

• Korean Journal of Oriental Medicine
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• v.5 no.1
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• pp.73-79
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• 1999

In this research we proceeded experiments to find the basis which make it possible to explain the physical and pathological process of Sasang constitutional medicine, in the way substituting hematopoietic-immune system(essence of life, blood, Ki and mental faculties : 精血氣神) Under these suppositions, the essence of life(精) is the multipotent stem cell which has the possibility to be specialized to any cell, the Ki(氣), blood(血) and mental faculties(神) are inferred that they are formed from specialized the essence of life(精), the blood(血) is the red blood cells and etc. that appears as the result of the genesis of circulation system. The Ki(氣) is from specialized basic immunity, the mental faculties(神) means long-term memories or combined immunity. Cytokines can act as specilaizing, growing factors and particiate in extremly combined procedure being controlled by both positive and negative specializing signals. Blood gathering was carried out in the morning and on empty stomach. The plasma was seperated and Erythropoietin, Stem cell factor, Granulocyte-colony stimulaing factor, Tumor necrosis factor, interlukin-3, Interleukin-6 were measured with ELISA kit. According to the result of post analysis by Duncan, each constitution is different in SCF(stem cell factor), IL-6(interleukin-6), EPO(erythropoietin). The value of Stem cell factor is high in order of Soumin(少陰人), Soyangin(少陽人), and Taeumin(太陰人), The value of interleukin-6 is high in Taeumin, Soumin, and Soyangin. Erythropoietin is high in order of Soumin, Soyangin, and Taeumin.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.453-462
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• 2020

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dose-dependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides- and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immune-enhancing agent acting via AMPK-NF-κB signaling pathway.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.4
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• pp.332-344
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• 1999

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Interleukin-8 (IL-8) is a neutrophil chemotactic factor that plays an important role in the recruitment of neutrophil to inflammatory loci. Inflammatory mediators by cells in the gingiva have been implicated in the initiation and progression of periodontitis and oral infection. The purpose of this study was conducted to investigate the effect of lipopolysaccharide (LPS), staphylococcus enterotoxin B (SEB) on production of IL-6 and IL-8 by human gingival and facial dermal fibroblasts. Primary cultured human gingival and facial dermal fibroblasts were incubated with LPS (0.01, 0.1, $1.0{\mu}g/ml$), SEB (0.01, 0.1, $1.0{\mu}g/ml$) or LPS $(0.1{\mu}g/ml)$ plus SEB $(0.1{\mu}g/ml)$. Culture supernatants were collected at 24, 48, and 72 hrs and assessed for IL-6 and IL-8 production by enzyme-linked immunosorbent assay. IL-6 production in gingival fibroblasts stimulated with LPS was higher than that with SEB. IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-6 production in facial dermal fibroblasts was increased only by stimulation with a high concentration of LPS $(1.0{\mu}g/ml)$. Its production in facial dermal fibroblasts by exposure with SEB was decreased in comparison with control, nontreated cells. Therefore, gingival fibroblasts showed higher sensitivity than facial dermal fibroblasts in response to low concentration of LPS. Also, IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in gingival fibroblasts was enhanced greatly only by stimulation of high concentration of LPS $(1.0{\mu}g/ml)$. That by exposure with SEB was increased only in 24 hrs cultivation. IL-8 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in facial dermal fibroblasts was decreased by LPS and increased only in 48 hrs cultivation by SEB. IL-8 production by double exposure with LPS plus SEB was enhanced only in 48 hrs cultivation in comparison with single exposure of LPS or SEB. therefore, IL-6 and IL-8 production were released at various quantities according to bacterial toxin applied and site of fibroblast harvested. These results suggest that gingival fibroblasts may be concerned with IL-6 and IL-8 related inflammatory response more than facial dermal fibroblasts.

• Clinics in Shoulder and Elbow
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• v.25 no.4
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• pp.296-303
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• 2022

Background: A previous study reported that hyperlipidemia increases the incidence of tears in the rotator cuff tendon and affects healing after repair. The aim of our study was to compare the gene and protein expression of torn rotator cuff tendons in patients both with and without hypercholesterolemia. Methods: Thirty patients who provided rotator cuff tendon samples were classified into either a non-hypercholesterolemia group (n=19, serum total cholesterol [TC] <200 mg/dL) and hypercholesterolemia group (n=11, serum TC ≥240 mg/dL) based on their concentrations of serum TC. The expression of various genes of interest, including COL1A1, IGF1, IL-6, MMP2, MMP3, MMP9, MMP13, TNMD, and TP53, was analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot analysis was performed on the proteins encoded by interleukin (IL)-6 and TP53 that showed significantly different expression levels in real-time qRT-PCR. Results: Except for IGF1, the gene expression levels of IL-6, MMP2, MMP9, and TP53 were significantly higher in the hypercholesterolemic group than in the non-hypercholesterolemia group. Western blot analysis confirmed significantly higher protein levels of IL-6 and TP53 in the hypercholesterolemic group (p<0.05). Conclusions: We observed an increase in inflammatory cytokine and matrix metalloproteinase (MMP) levels in hypercholesterolemic patients with rotator cuff tears. Increased levels of IL-6 and TP53 were observed at both the mRNA and protein levels. We suggest that the overexpression of IL-6 and TP53 may be a specific feature in rotator cuff disease patients with hypercholesterolemia.