• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5767-5772
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• 2014

Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${\kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${\gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${\gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${\kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${\gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${\kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${\kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${\gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${\gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${\gamma}$ and further activating the NF-${\kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${\gamma}$ and inhibition of expression of IL-10.

• The Journal of Internal Korean Medicine
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• v.27 no.4
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• pp.864-878
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• 2006

Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.1
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• pp.75-84
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• 2008

Colored potatoes are an excellent source of dietary polyphenols including anthocyanins. Generally, anthocyanins from fruits and vegetables exhibit anti-carcinogenesis and anti-cancer properties in vitro test. This experiment was conducted to know the effects of colored potato extracts contained anthocyanins on antimutagenic activity and anticancer activity to six human cancer cell lines containing LNCaP (androgen-dependent) prostate cancer cells. Extracts of three colored potatoes ('Hongyoung', 'Jayoung' and 'Jasim') and the white potato ('Superior') cultivars were used in this study. The extracts of three colored potatoes inhibited the mutagenicities induced by direct mutagen such as 4-nitro-quinoline-1-oxide (4-NQO) and another indirect mutagens of bezo(a)pyrene (BaP). Also, the extracts of 'Hoyoung' and 'Jayoung' showed higher antimutagenic activity than 'Jasim' and 'Superior' against to direct or indirect mutagen on both strains of TA98 and TA100. The activity of growth-inhibitory of extract of four potato cultivars were screened by SRB (sulphorhodamine B) method on diverse human cancer cells representing different types of cancers. Among the extract of four potato cultivars, the extract of 'Jasim' showed moderate inhibition on proliferation of LNCaP, ACHN and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. On the other hand, extract of 'Superior' did not inhibit the proliferation of any tested cancer cell lines. However, the extracts of 'Hongyoung and Jayoung' inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 2.5 to $30\;{\mu}g/mL$. On the basis of the $GI_{50}$ values, it is clear that LNCaP cells were more sensitive to extracts of colored potato cultivars than other cancer cells. The extract of 'Jayoung' at $30\;{\mu}g/mL$ were more active and inhibited cell proliferation, and induced apoptosis in LNCaP cells. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into source of antimutagenic and anticancer agent.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.227-233
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• 2004

Chronic exposure to solar radiation, particularly ultraviolet (UV) light, causes a variety of adverse reactions on human skin, such as sunburn, photoaging and photocarcinogenesis. Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage. And, repeated-UV irradiation activated the expression of the matrix metalloproteinase (MMP) and induced skin irritation. Therefore, the development of effective and safe photoprotectants that can reduce and improve the skin damage has been required. The purpose of this study was to investigate the photo-protective effect of several chinese medical plants (Juniperus chinensis) on the UV -induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. Fluorometric assays of the proteolytic activities of MMP-1 (collagenase) were performed using fluorescent collagen substrates. UVA induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. Expression of prostaglandin E$_2$ (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay(EIA) using PGE$_2$ monoclonal antibody. In the human skin we tested anti-irritation effect on the SLS-induced damage skin after appling the extract containing emulsion. We found that Juniperus chinensis extract had potent radical scavenging effect by 98% at 100$\mu\textrm{g}$/mL. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25$\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. In the test of proinflammatory cytokines of human keratinocytes Juniperus chinensis extract decreased expression of interleukin 6 about 30%. The amount of PGE$_2$ by HaCaT keratinocytes was significantly increased at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB (p < 0.05). At the concentrations of 3.2-25$\mu\textrm{g}$/mL of this extract, the production of PGE$_2$ by HaCaT keratinocytes (24 h after 10mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p < 0.05). In SLS-induced skin irritation model in vivo, we found to reduce skin erythema and improve barrier recovery after appling Juniperus chinensis extract containing emulsion when compared to irritated non-treated and placebo-treated skin. Our results suggest that Juniperus chinensis extract can be effectively used for the prevention of UV and SLS-induced adverse skin reactions and applied as anti-aging and anti-irritation cosmetics.

• Journal of Chest Surgery
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• v.31 no.5
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• pp.502-508
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• 1998

Proinflammatory cytokines such as tumor necrosis factor-$\alpha$(TNF-$\alpha$) have been implicated in myocardial and organ dysfunction associated with postperfusion syndrome. We tested the hypothesis that cytokine productions are depressed by preoperative cortiosteroid injection for cardiopulmonary bypass(CPB) and the postoperative courses will be better than without steriod pretreated cases. Cardiac surgery was performed in randomized blind fashion for 20 patients from June 1996 to September 1996. In the steroid group(n=10), corticosteroid(dexamethasone 1 mg/kg) was injected 1 hour before anesthetic induction, but in the control group(n=10), nothing was injected. Each of groups were sampled 11 times as scheduled for TNF-$\alpha$ bioassays. We have checked EKG, cardiac enzymes(CPK, LDH with isoenzyme), WBC count preoperative day, one day and three days after operation. Viatal signs were continuously monitored for three postoperaive days. In the postoperative period three patients in the control group had elevated body temperature and four patients had hypotension that required considerable intravenous fluid administration. But steroid injected patients showed normal body temperture and acceptable blood pressures without supportive treatment. CPK enzymes rose in control group higher than steroid group at postoperative 1st and 3rd day(CPK; 1122$\pm$465 vs 567$\pm$271, 864$\pm$42 vs 325$\pm$87), and CPK-MB enzymes rose in control group higher than steroid group at postoperative 1st day(106.4$\pm$115.1 vs 29.5$\pm$22.4)(P=0.02). Arterial tumor necrosis factor-$\alpha$ rose during cardiopulmonary bypass, peaking at 5 minutes before the end of aortic cross clamping(ACC-5min) in steroid group(11.9$\pm$4.7 pg/ml), and 5 minutes before the end of cardiopulmonary bypass(CPB-5min) in control group(22.3$\pm$6.8 pg/ml). The steroid pretreated patients had a shorter period of time in respirator suport time, ICU stay day, hospital admission day. We conclude that corticosteroid suppress cytokine production during and after cardiopulmonary bypass, and may improve the postoperative course through inhibition of reperfusion injury such as myocardial stunning and hemodynamic instability.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.128-139
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• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.