• Journal of Microbiology and Biotechnology
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• v.24 no.8
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• pp.1133-1142
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• 2014

Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory cytokines such as $TNF{\alpha}$, IL-$1{\beta}$, and IL-6 as well as chemokines. There are five splicing variants (${\alpha}$, ${\beta}$, ${\gamma}$, ${\delta}$, and ${\varepsilon}$) and IL-$32{\gamma}$ is the most active isoform. We generated human IL-$32{\gamma}$ transgenic (IL-$32{\gamma}$ TG) mice to express high level of IL-$32{\gamma}$ in various tissues, including immune cells. The pathology of sepsis is based on the systemic inflammatory response that is characterized by upregulating inflammatory cytokines in whole body, particularly in response to gram-negative bacteria. We investigated the role of IL-$32{\gamma}$ in a mouse model of experimental sepsis by using lipopolysaccharides (LPS). We found that IL-$32{\gamma}TG$ mice resisted LPS-induced lethal endotoxemia. IL-$32{\gamma}$ reduced systemic cytokines release after LPS administration but not the local immune response. IL-$32{\gamma}TG$ increased neutrophil influx into the initial foci of the primary injected site, and prolonged local cytokines and chemokines production. These results suggest that neutrophil recruitment in IL-$32{\gamma}TG$ occurred as a result of the local induction of chemokines but not the systemic inflammatory cytokine circulation. Together, our results suggest that IL-$32{\gamma}$ enhances an innate immune response against local infection but inhibits the spread of immune responses, leading to systemic immune disorder.

• BMB Reports
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• v.41 no.11
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• pp.814-819
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• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• Journal of Rheumatic Diseases
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• v.24 no.1
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• pp.14-20
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• 2017

Interleukin-32 (IL-32), a recently identified pro-inflammatory cytokine, is involved in the pathogenesis and progression of infections, cancer, chronic inflammation, and autoimmune disease. IL-32γ is the most active isoform in cell death and cell activation among nine distinct isoforms of IL-32. IL-32γ potentiates both osteogenic and osteoclastogenic capacities, and is critical in the coupling of bone resorption and bone formation for maintenance of bone homeostasis. IL-32γ is strongly associated with inflammatory bone disorders such as rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. In this review, we summarize current research on the role of IL-32γ in inflammatory bone disorders, highlighting this cytokine as a novel target for prognostic marker and control of these diseases.

• Parasites, Hosts and Diseases
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• v.34 no.3
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• pp.185-190
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• 1996

The TH cytokine responses of spleen cells stimulated with Con A from mice infected with Polasonimw westemcni were examined. The spleen cell culture supema- tants were assayed for TH1-specific $IFN-{\gamma}$ and TH2-specific IL-4. Cytokine responses for IL-4 peaked at three days ($410{\;}{\pm}{\;}60.9{\;}pg/ml$), persisted at a high level until the second week ($343{\;}{\pm}{\;}59.0{\;}pg/ml$), and then decreased slowly four and six weeks after infection. $IFN-{\gamma}$ production by splenocytes only increased during the first week ($151{\;}{\pm}{\;}32.3{\;}pg/ml$) and declined abruptly after the second week of infection. IFN- y production by splenocytes of infected mice was not observed during the sixth week of infection. In addition, serum IL-4 and $IFN-{\gamma}$ were measured. Serum IL-4 was not detected in substantial quantity until four to six weeks after infection. The time course of serum IL-4 was not correlated with that of IL-4 production by splenocytes. Serum $IFN-{\gamma}$ was undetectable during the entire course of infection. These results suggest that TH2 cytokine responses, rather than TH1, predominate in mice infected with P. westemcni.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.280-286
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• 2001

Epigallocathechin-3-gallate (EGCG), the main polyphenol component in green tea, inhibits angiogenesis, urokinase, and matalloproteinases, and EGCG also has the antioxidative property. Recent reports proposed that EGCG may modulate the immune response on allergy or asthma. Human nasal mucosal fibroblasts are a rich source of cytokines, inflammatory mediators, and chemokines. Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. The objective of this study was to investigate the effect of EGCG on the expression of the chemokines such as RANTES (regulated upon activation, normal T cell expressed and presumably secreted), eotaxin, and interleukin-8 (IL-8) in human nasal mucosal fibroblasts after stimulation with cytokines like IL-4, tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $interferon-{\gamma}\;(IFN-{\gamma})$. To detect the expression of chemokine genes, RT-PCR was performed. Expressions of RANTES, eotaxin, and IL-8 mRNA stimulated with IL-4 and $TNF-{\alpha}$ were increased, respectively, while the expression of those genes incubated with $IFN-{\gamma}$ was similar pattern compared to control group. Analyses of chemokine genes of cells pretreated with EGCG showed that the expressions of eotaxin, and IL-8 genes stimulated $IFN-{\gamma}$ were higher compared with those not pretreated with EGCG.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.323-333
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• 2011

Objectives : Zingberis Rhizoma (ZR) and Glycyrrihizae Radix (GR) have been widely used to prevent or treat allergic diseases. However, relatively little research has been conducted on the immune response to Senggang Gamcho-tang (SG) in a mixture of ZR and GR. The purpose of this study was to determine antiallergic effects of Senggang Gamcho-tang (SG) extracts ZR and GR on activity of murine splenocytes. Methods : This study was performed to investigate the effect of SG in mice, using in vitro experiments. Cells were treated with SG extract (1 ${\mu}g$/ml, 10 ${\mu}g$/ml and 100 ${\mu}g$/ml) plus Con A (2 ${\mu}g$/ml) and ZR (6.6 ${\mu}g$/ml and 66 ${\mu}g$/ml), GR (3.3 ${\mu}g$/ml and 33 ${\mu}g$/ml) respectively for 48 hrs. The production of IFN-${\gamma}$ and IL-4 were determined by ELISA. Results : No toxicity was found in splenocytes treated with SG extract for 48 hrs at the concentration of 0 ${\mu}g$/ml, 1 ${\mu}g$/ml, 10 ${\mu}g$/ml and 100 ${\mu}g$/ml, respectively. The production of IFN-${\gamma}$ increased to 23,968.7 pg/ml (p<0.001) while that of IL-4 significantly decreased to 14.1 pg/m l(p<0.05) only at the SG concentration of 100 ${\mu}g$/ml. With the GR concentration of 33 ${\mu}g$/ml in SG extract, the production of IFN-${\gamma}$ rose to 32,102.2 pg/ml (p<0.001) while that of IL-4 (p<0.05) declined to 34.2 pg/ml. However, there was no significant observation with regard to the effect of ZR on production of IFN-${\gamma}$ and IL-4. Conclusions : This study suggests an antiallergic effect of Senggang Gamcho-tang, which leads to the implication that SG extract may be used to enhance human immune function.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.25-32
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• 2015

Objectives : In this study, we investigated the effect of Cassia obtusifolia Linne (Cassiae Semen; CS) extract on ovalbumin (OVA)-induced allergic asthma in mice. Methods : CR was extracted with 70% ethanol. For in vitro study, HMC-1, human mast cells were treated with CS extract at 0.2 and $0.5mg/m{\ell}$ for 1 h, and then stimulated with compound (C) 48/80 for 30 min. Primary spleenocytes were isolated from the spleen of mice, treated with CS extract for 1 h, and then stimulated with ConA for 24 h. For in vivo study, mice were sensitized at day 0, 7 and 14 with 0.2% OVA and then airway challenged using neublizer at day 21, 23, 25, and 27 to induced allergic asthma. CS extract at doses of 100 and 300 mg/kg body weight was orally administered during OVA challenge once per a day. The levels of allergic mediators such as histamine, OVA-specific IgE, IL-4, and $IFN-{\gamma}$ were measured in the sera of mice or culture supernatants by EIA and ELISA, respectively. The expression of IL-4 and $IFN-{\gamma}$ gene was determined by RT-PCR. The histopathological change of lung tissues was observed with hematoxylin and eosin (H&E) and Periodic acid Schiff (PAS) staining. Results : The treatment of CS extract in HMC-1 cells significantly inhibited C48/80-induced degranulation, and histamine release. The treatment of CS extract in spleenocytes suppressed the expression of IL-4 and $IFN-{\gamma}$ mRNA. The administration of CS extract in OVA-induced asthmatic mice significantly decreased the levels of OVA-specific IgE, and IL-4 in a dose-dependent manner with OVA-control group. In addition, CS extract inhibited the infiltration of inflammatory cells and bronchiolar damage with epithelial thickening in lung tissues of OVA-induced asthma mice, and also mucin accumulation. Conclusions : These results indicate that CS extract prevents asthmatic damage through regulating the allergic immune response.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.32-41
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• 2010

Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

• The Journal of Korean Society for Radiation Therapy
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• v.9 no.1
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• pp.50-55
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• 1997

The optimal management of uveal melanoma is still a matter of controversy. To determine the effect of Gamma Knife surgery for patients with uveal malanoma. the authors reviewed the results of 5 patients underwent Gamma Knife sugery between Sep. 1993 and Dec. 1996. The mean age was 60.7 years ranging from 42.5 to 76.5 years. Median follow-up was 13.29 months and the patient with follow up period more than 6 months was 4. The mean tumor volume was $3442 mm^3$(mean diameter 15.3 mm) and all patients were irradiated with a mean maximum dose of 74Gy(range $60\~80\;Gy$), using the $50\%$ isodose. After Gamma Knife surgery. one pateint showed complete disapperance in tumor size with follow-up 32 months, one enucleation due to progression, and 2 no interval change. In regard to vision, one patient blind. one enucleation, and 2 patients had no interval change. According to our experiences, Gamma Knife surgery for uveal melanoma be able to achieve local tumor control, spare the eyeball, and have possibility of save vision.

• The Korean Journal of Food And Nutrition
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• v.32 no.3
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• pp.246-250
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• 2019

Nelumbo nucifera Gaertn has been usedas a traditional remedy and food source in South Korea. It promotes gastrointestinal function and controls blood pressures. Nelumbo nucifera Gaertn water extracts supplement at 5, 10, 50, 100, 250, 500, $1,000{\mu}g/mL$ after a 48 h pre-treatment with the mitogen (ConA or LPS) increased the mouse splenocytes proliferation. Water extract supplement also increased the cytokine production ($IL-1{\beta}$, $TNF-{\alpha}$ and $IFN-{\gamma}$), measured by a cytokine ELISA kit. For the result of in vitro study, the proliferation of splenocytes and cytokine production activated by peritoneal macrophages increased when water extracts were supplemented in the range of $50{\sim}500{\mu}L/mL$ concentration. Specifically, the levels of the splenocytes proliferation, $IL-1{\beta}$, $TNF-{\alpha}$ and $IFN-{\gamma}$ were the highest at $250{\mu}L/mL$ concentration. This in vitro study suggestedthat supplementation with Nelumbo nucifera Gaertn water extracts may enhance the immune function by regulating the splenocyte proliferation and enhancing the cytokine production activating macrophage in vitro.