• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.193-197
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• 2009

Suppressors of cytokine signaling (SOCS) proteins were originally identified as negative feedback regulators of cytokine signaling and include the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathways. Recent studies have shown that SOCS proteins negatively regulate the receptor tyrosine kinase (RTK) pathway including the insulin receptor (IR), EGFR, and KIT signaling pathways. In addition, SOCS1 and SOCS3 have been reported to have anti-tumor effects in human hepatocellular carcinoma (HCC). However, it is uncertain whether other members of the SOCS family are associated with tumor development and progression. In this study, to investigate whether SOCS6 is aberrantly regulated in HCC, we examined the expression level of SOCS6 in HCC by Western blot analysis and immunohistochemical staining. The results showed that SOCS6 was down-regulated in all examined HCCs compared to the corresponding normal tissues. In addition, expression of SOCS6 was observed in the cytoplasm of most normal and precancerous tissue, but not in the HCCs by immunohistochemical staining. This is first report to demonstrate that SOCS6 is aberrantly regulated in HCC. These findings suggest that underexpression of SOCS6 is involved in hepatocarcinogenesis, and SOCS6 may play a role, as a tumor suppressor, in HCC development and progression.

• International Journal of Oral Biology
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• 제33권4호
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• pp.163-177
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• 2008

Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 ($fimA^-$), CW120 ($ppk^-$) and KS7 ($relA^-$) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-$1{\beta}$ and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon-$\gamma$-inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.

• 대한한의학회지
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• 제31권2호
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• pp.91-108
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• 2010

Background & Objective: The aim of this study was to investigate the effect of P. radix on the inflammatory related gene expression in IL-$1{\beta}$-stimulated primary human gingival fibroblast using Whole Transcript Sense Target (WT-ST). Method: Human gingival fibroblast was incubated with P. radix [100 or $200\;{\mu}g/ml$], and IL-$1{\beta}$ [$1ng/m{\ell}$] added an hour later. After 24h, total RNA was extracted using RNeasy Mini Kit and the whole gene expression patterns were performed using WT-ST Labeling $Assay^{(R)}$. Result: In the DEG results, 782 genes were up-regulated in the IL-$1{\beta}$-treated group as compared to control and among those, 43 genes were associated with inflammation. 981 genes were down-regulated after treatment with IL-$1{\beta}$ and of those 7 genes were associated with inflammation. 1439 genes were up-regulated after treatment with P. radix plus IL-$1{\beta}$-treated when compared to IL-$1{\beta}$-treated alone group and 1225 genes were down-regulated in the same condition. Among the down-regulated genes, 5 were associated with inflammation- and inhibitor genes such as GDF15 and LIF. In the analysis of the P. radix plus IL-$1{\beta}$-treated group, the most significant pathways were the cytokine-cytokine receptor interaction, toll-like receptor signaling, JAK-STAT signaling and tyrosine metabolism. The gene expression patterns in the P. radix $200{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group appear to be more involved in the metabolism-related pathways than in the $100{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group. Conclusion & Discussion: By microarray analysis of gene expression data, we are able to identify gene expression patterns associated with not only anti-inflammation effect but also transcription function of P. radix.

• Journal of Acupuncture Research
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• 제25권3호
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• pp.41-51
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• 2008

Objectives : This study is to evaluate Effect of Inhibition Macrophage Migration Inhibitory Factor(MIF) activation by Hominis Placenta Herbal Acupuncture(HPA) on Rheumatic Arthritis(RA). Hominis Placenta is the placenta of healthy human, which is vital-strengthening medical stuff. In recent years, Hominis Placenta applied to chronic diseases because it makes us more resistance to diseases. Therefore it is supposed that HPA is effective on RA, a kind of autoimmune disease. When RA is induced, MIF is activated, too. MIF affects the process of inflammatory disease including RA. Methods : In order to investigate the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP(Matrix Metallo Proteinase)-9 mRNA expression by means of Reverse Transcriptase- Polymerase Chain Reaction(RT-PCR). In this study, we investigated the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP-9 mRNA expression by means of RT-PCR. Besides we investigated changing of MIF in synovial membrane and, Interleukin-6 receptor(IL-6R)-$\alpha$(pro-inflammatory cytokine), Signal transducers and activators of transcription(STAT)-3, MMP-9 after treating mouse, which is artificially attacked with RA, with HPA on its $ST_{35}$, LE201 in vivo. Results : 1. As a result of treating Lipopolysaccharide(LPS)-stimulated Raw246.7cell with HPA, MIF(RA related cytokine) and MMP-9 mRNA expression is reduced in vitro. And this reaction is concentration-dependatant. 2. In synovial membrane of the mice treated with HPA, inhibition of MIF, IL-6R-$\alpha$, STAT3 & MMP-9 activation is observed in vivo. Conclusions : From the above results, it might be suggested that HPA mitigate tissue damage originated from RA, because it intercepts the early process of by inhibition MIF activity.

• Animal Bioscience
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• 제36권3호
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• pp.521-528
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• 2023

Objective: This study investigated the effects of surgical castration on behavior, physiological and inflammatory indicators, and leukocyte cytokine mRNA levels in Korean cattle bull calves. Methods: Nineteen Korean cattle bull calves (average body weight, 254.5 kg; average age, 8.2 months) were divided into two treatment groups: control (n = 9) and castration (n = 10). Surgical castration was performed using Newberry knives and a Henderson castrating tool. Blood was obtained just before castration (0 h) and at 0.5 h, 6 h, 1 d, 3 d, 7 d, and 14 d after castration. Plasma cortisol (PC), saliva cortisol (SC), plasma substance P, and plasma haptoglobin concentrations, and the leucocyte mRNA levels of the interleukin-1-alpha (IL1A), interleukin-1-beta (IL1B), interleukin-1 receptor antagonist (IL1RN), and interleukin-6 (IL6) genes were analyzed. Results: Castration decreased (p<0.01) the average daily gain and gain/feed ratio. Castration reduced the time spent eating (p<0.001) and the eating frequency (p<0.01) and increased (p<0.001) the lying frequency. Castration temporarily increased (p<0.05) circulating PC and SC concentrations at 0.5 h after castration. Castration temporarily increased (p<0.05) plasma substance P concentrations at 1 d after castration. Castration increased (p<0.05) plasma haptoglobin concentrations at 1 and 3 d after castration. Castration increased (p<0.05) leukocyte mRNA levels of the IL1A, IL1B, IL1RN, and IL6 genes at 6 h after castration. Conclusion: Castration temporarily induced stress and expression of leucocyte inflammatory cytokine genes in Korean cattle bull calves.

• IMMUNE NETWORK
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• 제21권6호
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• pp.38.1-38.8
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• 2021

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

• IMMUNE NETWORK
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• 제14권1호
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• pp.14-20
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• 2014

CD28/T cell receptor ligation activates the NF-${\kappa}B$ signaling cascade during CD4 T cell activation. NF-${\kappa}B$ activation is required for cytokine gene expression and activated T cell survival and proliferation. Recently, many reports showed that NF-${\kappa}B$ activation is also involved in T helper (Th) cell differentiation including Th17 cell differentiation. In this review, we discuss the current literature on NF-${\kappa}B$ activation pathway and its effect on Th17 cell differentiation.

• 셀메드
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• 제6권3호
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• pp.16.1-16.5
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• 2016

Thymic stromal lymphopoietin (TSLP) is a novel interleukin (IL)-7-like cytokine and was originally discovered in the supernatant of a murine thymic stromal cell line. TSLP signal initiates via complex of the TSLP receptor and the IL-7 receptor α chain. TSLP expression is closely connected with many diseases such as atopic dermatitis, allergic rhinitis, asthma, inflammatory arthritis, eosinophilic esophagitis, rheumatoid arthritis, inflammatory bowel diseases, and cancer. In this review, I discussed biological roles of TSLP on mast cell-mediated allergic responses. In addition, this review summarizes the effective drugs in allergic-inflammatory reactions induced by TSLP on mast cells.

• Journal of Periodontal and Implant Science
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• 제32권4호
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• pp.865-873
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• 2002

The primary cause of tooth loss after 30 years of age is periodontal disease. Destruction of alveolar bone by periodontal disease is done by bone resorbing activity of osteoclasts. Understanding differentiation and activation mechanism of osteoclasts is essential for controling periodontal disease. The purpose of this study is to identify the possible effects of Vitamin D and cytokines affecting osteoclasts and its precursor cells. Four to six week-old mice were killed and humerus, radius, tibia and femur were removed aseptically and washed two times with Hank's solution containing penicillin-streptomycin and then soft tissue were removed. Bone marrow cells were collected by 22 gauge needle. Cells were cultured in Hank's solution containing 1 mg/ml type II collagenase, 0.05% trypsin, 41mM EDTA. Supernatant solution was removed 5 times after 15 minutes of digestion with above mentioned enzyme solution, and remained bone particles were maintained in alpha-MEM for 15 minutes and $4^{\circ}C$ temperature. Bone particles were agitated for 1 minute and supernatant solution containing osteoclast precursor cells were filtrated with cell stainer. These separated osteoclast precursor cells were dispensed with 100-mm culture dish by $1{\times}10^7$ cells unit and cultured in ${\alpha}$- MEM containing 20 ng/ml recombinant human M-CSF, 30 ng/ml recombinant human soluble osteoclast differentiation factor and 10% fetal calf serum for 2 and 7 days. Total RNA of osteoclast precursor cells were extracted using RNeasy kit. One ${\mu}g$ of total RNA was reverse transcribed in $42^{\circ}C$ for 30 minutes using SuperScriptII reverse transcriptase. Expression of transcribed receptors of each hormone and cytokine were traced with 1 ${\mu}l$ of cDNA solution by PCR amplification. Vitamin D receptor WAS found in cells cultured for 7 days. TNF-${\alpha}$ receptor was found in cells cultured for 2 days and amount of receptors were increased by 7 days. IL-1 type I receptor was not found in cells cultured 2 and 7 days. But, IL-1 receptor type II was found in cells cultured for 2 days. TGF-${\alpha},{\beta}$type I receptor was found in cells cultured 2 and 7 days, and amount of receptors were increased by 7 days of culture. These results implies Vitamin D and cytokines can affect osteoclasts directly, and affecting period in differentiation cycle of osteoclasts is different by Vitamin D and cytokines.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.279-282
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• 2003

To investigate the effect of fluoxetine, one of selective serotonin reuptake inhibitors (SSRIs), on the immune system, human peripheral blood mononuclear cells (PBMC) were treated with fluoxetine $(10^{-7}\;M)$ for 24 h, and immune-related genes were analyzed by cDNA microarray. Expression of the immunerelated genes such as CD107b (LAMP-2), CD47 receptor (thrombospondin receptor), CD5 antigen-like (scavenger receptor cysteine rich family), copine III (CPNE3), interleukin (IL)-18 (interferon-gammainducing factor), integrin alpha 4 (CD49d), integrin alpha L subunit (CD11a), IL-3 receptor alpha subunit, L apoferritin, and small inducible cytokine subfamily A (Cys-Cys) member 13 (SCYA13) was induced by fluoxetine. This result suggests that fluoxetine may affect the immune system, and provides fundamental data for the involvement of SSRIs on immunoregulation.