• Food Science and Biotechnology
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• 제14권4호
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• pp.479-486
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• 2005

Arabinoxylan, a complex polysaccharide in cereal cell walls, has recently received research attention as a biological response modifier. The immunomodulating effect of arabinoxylans from rice bran (AXrb) was studied using a combined process of extrusion and commercial hemicellulase treatment in order to elucidate the augmentation mechanism of cell-mediated immunity in vitro. The cytotoxicity of mouse spleen lymphocytes against YAC-1 tumor cells was significantly enhanced by treatment with AXrb at $10-100\;{\mu}g/mL$. In an attempt to investigate the mechanism by which AXrb enhance NK cytotoxicity, we examined the effect of AXrb on cytokine production by spleen lymphocytes. Culture supernatants of the cells incubated with AXrb were collected and analyzed for IL-2 and IFN-${\gamma}$ synthesis by ELISA. IL-2 and IFN-${\gamma}$ production were increased significantly. These results suggest that AXrb may induce Th1 immune responses. Macrophages play an important role in host defenses against tumors by killing them and producing secretory products, which protect against bacterial, viral infection and malignant cell growth. AXrb were examined for their ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various concentrations ($10-100\;{\mu}g/mL$) of AXrb, AXrb induced tumoricidal activity, as well as increasing phagocytosis and the production of NO, $H_2O_2$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results indicate that reactive oxygen species, reactive nitrogen species, and inflammatory cytokines are likely to be the major mediators of tumoricidal activity in AXrb-treated macrophages. Therefore, AXrb may be useful in cancer immunotherapy and it is anticipated that AXrb obtained using extrusion and subsequent enzyme treatment can be used as an ingredient in nutraceuticals and cereal-based functional food.

• 한국식품영양학회지
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• 제26권3호
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• pp.375-382
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• 2013

The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at $100^{\circ}C$(OeE-100). OeE-100 doses up to $62.5{\mu}g/m{\ell}$ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous ($4{\sim}100{\mu}g/mouse$) or oral (2 mg/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-${\alpha}$, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 ($10{\sim}100{\mu}g/mouse$) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 ($100{\mu}g/mouse$) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.394-402
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• 2008

Atopic dermatitis (AD) is an inflammatory skin disease commonly characterized by infiltration of inflammatory cells into skin lesions. Keratinocytes produce many chemokines that are involved in the pathogenesis of skin disorders. In particular, macrophage-derived chemokine (MDC/CCL22) and thymus and activationregulated chemokine (TARC/CCL17) are Th2-type cytokines. Serum MDC and TARC levels are increased in AD patients. In this study, we investigated the anti-inflammatory effect and mechanism of action of the active fraction from Prunus yedoensis bark. We evaluated their inhibitory effects on the AD-like inflammatory markers (MDC and TARC) and JAK-STAT pathway (STAT1) in HaCaT keratinocytes. The EtOAc fraction of the crude extract (80% EtOH) and the E5 sub-fraction potently inhibited the induction of MDC and TARC mRNA and protein at 50 ${\mu}g$/mL in HaCaT cells. In addition, the E5 sub-fraction inhibited the phosphorylation of STAT1 protein associated with IFN-$\gamma$ signaling transduction in a dose-dependent manner. Thus, P. yedoensis may have antiatopic activity by suppressing the inflammatory chemokines (MDC and TARC).

• Archives of Pharmacal Research
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• 제27권5호
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• pp.531-538
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• 2004

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-a, IL-1$\beta$, IL-2, IL-6, IL-12, IFN-${\gamma}$ and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1$^{st}$-5$^{th}$ days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7-2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.d.

• Journal of Ginseng Research
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• 제37권2호
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• pp.167-175
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• 2013

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL-5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.

• 대한본초학회지
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• 제28권1호
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• pp.65-71
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• 2013

Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

• 한방안이비인후피부과학회지
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• 제32권3호
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• pp.58-76
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• 2019

Objectives : This study was designed to examine the effects of Daecheonglyong-tang(DCL) on atopic dermatitis induced by DNCB in mice Methods : The Nc/Nga mice were divided into 5 groups, and four groups excluding the normal group were applied by 2,4-dinitrochlorobenzene(DNCB), to cause AD and were orally administered with distilled water(negative control), dexamethasone(positive control), and DCL 200 or 400mg/kg once a day for 4 weeks respectively. The visual changes on skin, changes in skin tissue thickness and eosinophil infiltration were observed. IgE, Histamine, Cytokines, immune cells and the amount of gene expression of filaggrin, VEGF, $TGF-{\beta}1$, EGF were measured. Results : Dermatitis score showed a gross improvement on all DCL groups, similar to or better than positive control. All DCL groups showed no significant change in the basophils, while neutrophils and eosinophils decreased. In only DCL 400 mg/kg groups, white blood cells and mononuclear cells were decreased and lymphocytes were increased. In particular, neutrophils had similar or better effects than the positive control. In all DCL groups, IgE, Histamine, $IL-1{\beta}$, IL-4, IL-5, IL-6 and $TNF-{\alpha}$ were decreased and IL-2 was increased. In only DCL 400 mg/kg groups, IL-10 decreased and $IFN-{\gamma}$ increased. In particular, $IL-1{\beta}$ and $IFN-{\gamma}$ showed a similar rate of increase and decrease comparing positive control in DCL 400 mg/kg. $TGF-{\beta}$1 was increased in all DCL groups, filaggrin and VEGF were increased in only DCL 400 mg/kg groups. EGF did not make any changes. Epidermis, dermis thickness and eosinophil infiltration were also decreased in all DCL groups. Conclusions : By increasing Th1 cytokine and decreasing Th2 cytokine, DCL extracts appear to be effective in controlling immune response imbalances, anti-inflammatory and skin regeneration and are likely to be available as a treatment for AD.

• Journal of Applied Biological Chemistry
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• 제63권1호
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• pp.95-101
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• 2020

건선(psoriasis)은 인체 피부조직 중 표피의 과증식 및 다양한 크기의 홍반, 인설 등이 동반되는 난치성 자가면역 피부질환이다. 건선 피부염 발병 기작은 명확히 규명되지 않았으나 각질 형성세포의 과분화 과정에 관여하는 염증성 cytokine과 Th17 세포를 포함한 면역세포를 염증부위로 유인하는 chemokine (C-C motif) ligand 20 (CCL20)이 발병과정에 관여하는 것으로 알려진다. 따라서 건선치료에 효과적인 천연 소재를 발굴하기 위해 예로부터 항염증 활성이 알려진 익지인(Alpiniaoxyphylla Miquel)의 유효성분인 yakuchinone-A의 건선 피부염 개선효과를 연구하였다. 먼저 CCK-8 assay 통해 human keratinocyte (HaCaT) 세포에 tumor necrosis factor-alpha (TNF-α)와 yakuchinone-A를 동시 처리하여 세포독성을 관찰한 결과, yakuchinone-A는 10 ㎍/mL까지 세포독성이 관찰되지 않았다. TNF-α를 HaCaT 세포에 처리하여 염증을 유발한 후 yakuchinone-A를 농도별로 처리한 결과 IL-6, IL-8, TNF-α 등 건선 피부염 유발 cytokine의 mRNA 발현이 각각 61.4±7.5, 23.6±1.5, 46.0±4.8% 수준으로 감소하였고, Th17 세포를 유인하는 chemokine인 CCL20 또한 yakuchinone-A에 의해 유의적으로 억제되었다. 또한 CCL20 발현에 관여하는 NF-κB/IκB pathway에서 IκB 인산화 및 STAT3 인산화가 yakuchinone-A에 의해 79.1±5.0, 80.8±2.3% 수준만큼 농도 의존적으로 억제되었다. 마지막으로 Th17 세포에 의해 분비되는 IL-17A에 의해 활성화된 HaCaT 세포에 yakuchinone-A를 처리한 결과, CCL20 mRNA발현이 농도의존적으로 감소하였다. 이러한 결과들을 토대로 yakuchinone-A는 건선 피부염 개선 활성을 가지며, 향후 새로운 건선 피부염 개선 소재로 개발될 수 있을 것으로 기대된다.

• 한방안이비인후피부과학회지
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• 제19권2호
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• pp.1-18
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• 2006

Objective : Although management of asthma has become increasingly effective, its cure remains elusive, necessitating a new modality to prevent or eliminate causes triggering clinical progress. Based in the clinical experiences, a novel decoration Cheongsangbiyeum (CSB), has been developed to treat asthma, which consists of Polyporus, Semen Myristicae, Pericarpium citri Reticulatae, Rhizoma Cimicifugae, Cortex Albizziae, Fructus Rubi, Rhizoma Zedoariae, and Rhizoma Rhei. In the current study, its anti-asthmatic efficacy was evaluated using a mouse model of asthma. Methods : Experimental allergic asthma was induced by repeated intraperitioneal sensitization and intranasal challenge of ovalbumin (OVA). Water extract of CSB (1 mg/mouse/day) was administrated orally whereas control mice on given with identical volume of phosphate-buffered saline (PBS) for 5 days during the course of antigen challenge. When airway hyperreactivity(AHR) measured by ${\bata}-methacoline-induced$ airflow obstruction was compared, AHR of CSB-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and eosinophils was also markedly reduced by CSB treatment suggesting that oral treatment of CSB can alleviate the airway inflammation. For a better understanding of possible mechanisms underlying anti-asthmatic effet of CSB, cytokine (IL-4, IL-5, IL-13 and $IFN{\gamma}$ levels in bronchoalveola lavage fluid (BALF) and lung tissues were determined. Results : The results showed that cytokine levels were significantly lowered by CSB treatment. Additionally, number of draining lymph node cells was significantly lower than those of control mice. These data indicate that CSB suppress in vivo allergen-specific response. However, notably, levels of type 2 cytokines such as IL-5 and IL-13 were more profoundly influenced. Moreover, in vitro OVA-specific proliferative response and type 2 cytokine (IL-4, IL-5 and IL-13) production lymph node cells was markedly decreased in CSB-treated mice, whereas their $IFN{\gamma}$ production was not significantly altered Thrse data clearly showed a preferential inhibition of type 2 T cell (Th2) response by CSB treatment. This finding was also supported by serum antibody data showing that levels of OVA-specific type 2 antibodies, IgE and IgG1, in CSB-treated mice were significantly lower than in control mice, while type 1 antibody, IgG2a level m rather higher than controls, although the difference was in significant. Conclusions : In conclusion, oral administration of CSB attenuates asthmatic manifestations including AHR ad airway recruitment of eosinophils in a mouse model which possibly results from selective inhibition of Th2 cell response to allergen. Our data suggest a potential clinical application of CSB for control of allergic asthma.

• IMMUNE NETWORK
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• 제3권1호
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• pp.1-7
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• 2003

Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.