• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.452-456
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• 2009

The purpose of this study was to investigate the anti-inflammatory effects and cellular mechanism of piperine on murine peritoneal macrophages. To evaluate the effects of piperine, we examined the production of nitric oxide (NO), interleukin (IL)-10 and IL-12. To investigate inhibitory mechanism of piperine, we examined the MAPKs and Ik-Ba in murine peritoneal macrophages, Piperine itself does not have any cytotoxic effect and reduced lipopolysaccharid (LPS), Poly(I:C), CpG-ODN -induced production of NO, IL-10 and IL-12 in peritoneal macrophages. Piperine inhibited the activation of extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK 1/2) not the activation of p38 and the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated murine peritoneal macrophages.ln conclusion, Piperine down-regulated LPS-induced production of NO, IL-10 and IL-12, which could provide a clinical basis for anti-inflammatory properties of piperine.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.38-43
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• 2004

Backgroud: Immunotherapy using dendritic cells (DC) loaded with tumor antigens may represent a potentially effective method for inducing antitumor immunity. We evaluated the effectiveness of DC-based antitumor immune response in various conditions. Methods: DC were cultured from peripheral blood mononuclear cells (PBMNC) in myelogenous leukemia (ML) and lysates of autologous leukemic cells are used as tumor antigen. The effectiveness of interleukin-12 (IL-12) and CD40L (CD154) on the antigen presenting function of lysates-loaded DC was analyzed by proliferation, cytokine production, and cytotoxicity tests with activated PBMNC (mainly lymphocytes). For generating antigen-loaded DC, direct fusion of DC with ML was studied. Results: Antigen loaded DC induced significantly effective antitumor immune response against autologous leukemic cells. Administration of IL-12 on the DC based antitumor immune response showed higher proliferation activity, IFN-$\gamma$ production, and cytotoxic activity of PBMNC. Also, fused cell has a potent antitumor immune response. Conclusion: We conclude that lysates-loaded DC with IL-12 may be effectively utilized as inducer of antitumor immune reaction in ML and in vivo application with DC-based antitumor immunotherapy or tumor vaccination seems to be feasible.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.140-153
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• 2003

Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

• Molecules and Cells
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• v.20 no.2
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• pp.288-296
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• 2005

Cytokines interleukin (IL) 12 and 23 play critical roles in linking innate and adaptive immune responses. They are members of heterodimeric cytokines, sharing a subunit p40. Although IL12/23 p40 is mainly induced in macrophages and dendritic cells (DCs) after stimulation with microbial Toll-like receptor ligands, methods to monitor the cells that produce IL12/23 p40 in vivo are limited. Recently, the mouse model to track p40-expressing cells with fluorescent reporter, yellow fluorescent protein, has been developed. Macrophages and DCs from these mice faithfully reported p40 induction using the fluorescent marker. Here we took advantage of these reporter mice to screen bio-compounds for p40-inducing activity. After screening hundreds of compounds, we found several extracts inducing IL12/23 p40 gene expression. Treatment of DCs with these extracts induced the expression of MHC class II and co-stimulatory molecules, which implies that these might be useful as adjuvants. Next, the in vivo target immune cells of candidate compounds were examined. The reporter system can be useful to identify cells producing IL12 or IL23 in vivo as well as in vitro. Thus, our cytokine reporter system proved to be a valuable reagent for screening for immunostimulatory molecules and identification of target cells in vivo.

• Advances in Traditional Medicine
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• v.6 no.2
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• pp.134-143
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• 2006

The capacities of bacterial DNA, extracted from Salmonella typhimurium, and lipopolysaccharide (LPS), extracted from Salmonella minnesota, to activate mouse peritoneal macrophages in vitro were compared. Activation was assessed by estimating e levels of 3 cytokines, IL-10, IL-12, and $IL-1{\beta}$, at time intervals of 3, 6, 9, and 24 h after addition of LPS and/or DNA to macrophage cultures. Cytokine levels in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA) and cytokine mRNA levels were estimated based on band intensity in cultured cells by reverse transcriptase-polymerase chain reaction (RT-PCR). Results obtained demonstrated the ability of DNA and LPS to elicit increased production of all 3 cytokines as compared to controls. In the amount tested, LPS appeared to be a more potent inducer of IL-12, and $IL-1{\beta}$, whereas DNA induced higher levels of IL-10. DNA and LPS, used in combination, exhibited neither an additive nor a synergistic effect. Rather, an antagonist effect appeared to occur. RT-PCR results correlated well with ELISA.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.898-904
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• 2003

Pellinus linteus has been used for the prevention of cancer traditionally. There are three origins of Pellinus linteus, Korea, China and Cambodia. However, their immunological activities were not evlauated comparatively. Thus, this study was done to evaluate immunomodulatory effects of Phellinus linteus(PL) from Korea, china and cambodia, We confirmed PL showed two major protein bands, 50 kDa and 80 kDa by protein analysis. These PL effectively upregulated the expressions of IL-2 at 10 ug/ml and GM-CSF, IL-4, IL-10, IL-12(p35), IL-12(p40), IL-18, IFN-r in all concentrations. However, Korea-PL upregulated the expression of IL-12 more effectively than the other PLs. It intended to increase NO with no significance. Those results indicate Phellinus linteus had cytokine modulating effect

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.130-138
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• 2005

This experiment was designed to investigate the effect of Phellodendron amurense(PLDA) on the Alzheimer's disease. The effects of PLDA extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. PLDA extract suppressed $IL-1{\beta}$, IL-6, APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ ; AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$. PLDA extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. PLDA extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that PLDA extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Korean Journal of Acupuncture
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• v.26 no.3
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• pp.55-68
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• 2009

Objectives : To investigate the anti-inflammatory effects of Scutellaria baicalensis Georgi pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods : Sprague-Dawley rats were divided into 4 groups; LPS control (n=6), LPS+Scutellaria baicalensis Georgi pharmacopuncture at BL23 (n=6, BL23), LPS+Scutellaria baicalensis Georgi pharmacopuncture at CV12 (n=6, CV12), and LPS+Scutellaria baicalensis Georgi pharmacopuncture at GV4 (n=6, GV4). Pharmacopuncture was given every two days for 4 weeks followed by inflammation induction by intraperitoneal LPS injection (5mg/kg). Blood, liver tissue, and peritoneal lavage fluid were taken and proinflammatory cytokines and other related factors were analysed. Results : For proinflammatory cytokines, CV12 pharmacopuncture group was significantly different compared with the control group in plasma IL-$1{\beta}$, IL-6, TNF-$\alpha$, and IL-10 5 h after LPS injection (P<0.05). For plasma IL-$1{\beta}$ and IL-6, CV12 pharmacopuncture group also showed significant difference at 2 h compared with the control (P<0.05). GV4 pharmacopuncture group was significantly different compared with the control at 5 h in plasma IL-$1{\beta}$, IL-6, and TNF-$\alpha$ and at 2 h in IL-10 (P<0.05). Liver cytokines were analyzed at 5 h after LPS injection; only CV12 pharmacopuncture group showed significant difference in IL-$1{\beta}$ (P<0.05) and others including IL-6, TNF-$\alpha$, and IL-10 had no difference compared with the control group. CD4/CD8 ratio and the phagocytic activities of polymorphonuclear neutrophils were not different from those of control group in all pharmacopuncture groups (P>0.05). Plasma NO3-/NO2- and intracellular adhesion molecule-1 of CV12 pharmacopuncture group were significantly lower than that of the control group (P<0.05). In the plasma concentration of prostaglandin E2, all 3 pharmacopuncture groups had significantly lower values than that of the control group (P<0.05), but there was no difference among pharmacopucnture groups. Monocyte chemoattractant protein-1 and cytokine-induced neutorphil chemoattractant-1 in peritoneal lavage fluid was significantly decreased in CV12 pharmacopuncture group compared with the control group (P<0.05). Conclusions : These results indicate that Scutellaria baicalensis Georgi pharmacopuncture at CV12 may have a potent anti-inflammatory effect in an LPS-induced inflammatory rat model.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.631-636
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• 2008

Acanthopanax divaricatus var. albeofructus (ADA) have been shown to have various levels of activity such as antioxidant, anticancer, antivirus, and immunostimulatory effects. However, little is known about its mechanism related to the modulation of immune activities. In this study, a water extract of ADA leaves were used to treat human peripheral blood mononuclear cells (hPBMC) to determine the underlying mechanisms for the immunostimulatory effects. To characterize its immunomodulatory activity, the secretion level of various cytokines including IL-2, IL-4, IL-6, IL-10, IL-12, IFN-$\gamma$, and TNF-$\alpha$ were measured using enzyme-linked immunosorbent assay (ELISA). Treatment of hPBMC with ADA leaf extract in an in vitro experiment induced various Th1 cytokines in a dose-dependent manner. A significant increase of IL-2, IL-12, IFN-$\gamma$, and TNF-$\alpha$ secretion was observed in the presence of ADA leaf extract. In contrast, Th2 cytokines including IL-4 and IL-6 were suppressed. There was no significant change in IL-10 release. Our results showed an increase in Th1 and a decrease in Th2 cytokine secretion which suggests that ADA may influence the immune response towards a predominance of Th1 cytokines in the immune system.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.211-218
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• 2010

Acanthopanax koreanum Nakai (Araliaceae) is a medicinal plant indigenous to Korea. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. In our study, three lignans, eleutheroside E (EE), tortoside A (TA), and syringaresinol (SY), were isolated from the stem and root of A. koreanum in an effort to study the immunomodulating effect. We treated natural killer cells and dendritic cells with lignans (EE, TA, or SY), and analyzed their cytokine (IL-12 and IFN-${\gamma}$) secretion. EE, TA, or SY markedly enhanced IL-12 secretion in mouse lymphoid (DC1) and myeloid type (DC2.4) dendritic cells after 48 hr of treatment. There were no significant differences in the cytokine stimulatory effects between EE, TA, or SY. Moreover, treatment of EE, TA, or SY significantly induced IFN-${\gamma}$ secretion by human NK cells (NK92MI) confirmed by ELISA assay. This study suggests that lignans from A. koreanum modulate cytokines, and that such modulation may provide the mechanism of action for many of their therapeutic effects.