• 한국약용작물학회지
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• 제26권1호
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• pp.8-18
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• 2018

Background: This present study was conducted to evaluate the anti-inflammatory and immune regulatory effects of Aucklandia lappa Decne (AL). Methods and Results: We measured cytotoxicity, nitric oxide (NO) content, mRNA expression (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$), protein expression (iNOS, COX-2, and $I{\kappa}B$) and phagocytic activity in RAW264.7 cells. Male BALB/c mice were fed 100 mg/kg AL (Aucklandia lappa Decneon 70% ethanol extract) and 250 mg/kg AL for 4 weeks; thereafter, we observed B/T or $CD4^+/CD8^+$ lymphocyte subpopulation change, and expression patterns of $CD4^+$ and $CD8^+$ lymphocytes by immunohistochemical staining in mouse splenocytes and/or thymocytes. To determine the experimental concentration of AL, cell viability was measured by MTT assay and tested at $12.5{\mu}g/m{\ell}$ or less. AL inhibited the levels of NO, lymphokine production (IL-$1{\beta}$, and TNF-${\alpha}$), and mRNA (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$) and protein (iNOS, and COX-2) expression. Additionally, the levels of $I{\kappa}B$, phagocytic activity, and splenic and thymic T lymphocytes, especially $T_H$ and $T_C$ cells were significantly increased in AL administered mice. The immuno-reactive density of $CD4^+$ and $CD8^+$ lymphocytes was stronger in AL groups than in the normal group. AL stimulated NO, iNOS, and COX-2, and regulated IL-1${\alpha}$, IL-$1{\beta}$, TNF-${\alpha}$, and $I{\kappa}B$ in macrophages treated with LPS (lipopolysaccharide). In addition, AL increased the phagocytic activity of macrophages and the immunity of mouse T ($T_H$, and $T_C$) cells. Conclusions: These results suggested that AL might show anti-inflammatory activity via the suppression of various inflammatory markers and immuno-regulatory activity.

• 동의생리병리학회지
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• 제20권2호
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• pp.420-427
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• 2006

Immunological activities of the combined-administration of Ginseng Radix Rubra and Vitis Fructus were examined in C57BL/6 mice. Ginseng Radix Rubra and Vitis Fructus were extracted with distilled water or 40% ethyl alcohol. Ginseng Radix Rubra water extracts (GW), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:1)], the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:3)], 40% ethyl alcohol extracts of Ginseng Radix Rubra (GE), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:1)] and the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:3)] were administered p.o. once a day for 7 days, respectively. GVW(1:1) and GVW(1:3) decreased the viability of thymocytes increased by GW, but GVE(1:1) and GVE(1:3) increased the viability of thymocytes decreased by GE. GVW(1:1) and GVW(1:3) increased the viability of splenocytes decreased by GW or GE. Also, GVW(1:1) and GVE(1:1) enhanced the population of helper T cell in thymocytes, and GVE(1:1) and GVE(1:3) decreased the population of cytotoxic T cells increased by GE. Furthermore, GVW(1:1), GVW(1:3), GVE(1:1) and GVE(1:3) enhanced the population of $B220^+$ cells decreased by GW or GE, and decreased the population of $Thyl^+$ cells increased by GW or GE, and decreased the population of splenic $CD4^+$ cells increased by GW or GE. In addition, GVW(1:1) and GVW(1:3) decreased the phagocytic activity and the production of nitric oxide in peritoneal macrophages increased by GW, but GVE(1:1) and GVE(1:3) enhanced the phagocytic activity and the production of nitric oxide in peritoneal macrophages decreased by GE. These results suggest that Vitis Fructus has an regulative action on immune response of Ginseng Radix Rubra.

• Natural Product Sciences
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• 제13권3호
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• pp.207-213
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• 2007

Scutellaria baicalensis is known as a herbal medicine with anti-inflammatory and anti-oxidative activities. However, effect of Scutellaria baicalensis on lupus pathogenesis that is characterized by overproduction of proinflammatory cytokines and abnormalities in regulation, function, and interaction of immune cells remains unclear. We investigated effects of Scutellariae radix methanol extract (SBMeOH) on the production of proinflammatory cytokines and abnormal activation of T cells in vitro in pristane-induced lupus BALB/c mice. These results demonstrated that SBMeOH significantly decreased the LPS-stimulated production of $TNF-{\alpha}$, IL-6, and IL-10 by splenic and peritoneal macrophages and IL-6 and IL-10 by splenocytes from pristane-induced lupus mice. SBMeOH significantly downregulated the Con A-stimulated overproduction of IL-6, IL-10, and $IFN-{\gamma}$ by splenocytes from pristane-induced lupus mice. Also, SBMeOH significantly attenuated the Con A-induced expression of CD4+ T cells and CD69+CD4+ T cells but not CD8+ T cells in pristane-induced lupus mice. Our findings indicate that SBMeOH may ameliorate lupus pathogenic inflammation and autoimmunity via downregulation of proinflammatory cytokine production and abnormal activation of T cells.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.446-454
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• 2009

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-$\alpha$. In the present study, adverse effects of FPP-3 on immune functions were determined in female BALB/c mice. When mice were administered orally with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days, FPP-3 suppressed the number of antibody-forming cells and reduced thymus weight at 500 mg/kg. In addition, FPP-3 administered mice exhibited reduced splenic cellularity and numbers of splenocyte subsets, such as $CD3^+$ cells, $CD3^+CD4^+$ cells, $CD3^+CD8^+$ cells and macrophages. IL-4 mRNA expression was significantly suppressed by FPP-3 treatment. Moreover, the number of $CD4^+IL-4^+$ cells was reduced following the treatment of mice with 500 mg/kg of FPP-3. These results suggested that FPP-3 at 500 mg/kg might be immunotoxic, and that FPP-3-induced immunotoxicity might be mediated, at least in part, through the inhibition of cytokine production, such as IL-4.

• 동의생리병리학회지
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• 제18권6호
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• pp.1869-1880
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• 2004

In the oriental medicine, a mixture of herbs has been commonly used as important components to control allergic and inflammatory diseases. In the present study, we prepared a mixture of Dictamni Radicis Cortex(Baiksunpee), Houttuyniae Herba(Uhsungcho), and Aurantii Immaturus Fructus(Jisil) to examine its anti-allergic effects in activated mouse splenic cells and found that Mix-1 is involved in regulating levels of B cell activating factors (CD23 and CD11a), IL-1β, IL-6, IL-10, TNF-α, and 1gE as well as HRF expression. It was observed that Mix-1 did not have cytotoxic effects on mLFC. Mix-1 showed inhibition of CD23 and CD11 alpaha expression in mouse B cells, and also decreased the production of IL-6, TNF-α, and 1gE. Both RT-PCR and ELISA analyses indicated that IL-6 and TNF alpha production were regulated at the gene expression level. In contrast, IL-10 mRNA and protein levels were increased in activated B cells by Mix-1 treatment. We also found that Mix-1 inhibited B cell proliferation and inhibited histamine releasing factor(HRF) expression, suggesting its inhibitory effect on histamine secretion. These data indicated that Mix-1 has an anti-allergic effect in activated macrophages and further suggest the possible application of Mix-1 as a therapeutic agent for the treatment of allergy-related diseases.

• Parasites, Hosts and Diseases
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• 제40권3호
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• 한국수산과학회지
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• 제50권3호
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• pp.302-310
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• 2017

Interferon regulatory factor 8 (IRF8) is essential for the development of B and T cells, as well as for the activity of dendritic cells and macrophages. We performed molecular characterization of IRF8 from rock fish, Sebastes schlegelii (Ss), and investigated the spatial and temporal profile of mRNA expression after challenge with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C), or Streptococcus iniae. The full-length cDNA sequence of SsIRF8 was 1,657 bp, containing an ORF of 1,266 bp. The gene had a predicted molecular mass of 47.7 kDa and an isoelectric point of 5.99. The amino acid sequence coded by this gene showed the highest degree of identity (90.8%) and similarity (96.2%) with IRF8 from Oplegnathus fasciatus. The SsIRF8 mRNA was expressed ubiquitously, at varying levels, with the highest level of expression observed in the spleen. To confirm the role of SsIRF8 in mediating the immune response, we measured SsIRF8 mRNA expression in the splenic tissue at different time points after injection with LPS, poly I:C, or S. iniae. The qRT-PCR results showed that SsIRF8 mRNA expression in the poly I:C-injected group was highly upregulated 6 hr after exposure (P<0.05). Expression of SsIRF8 mRNA in the S. iniae-injected group peaked at 24 hr. These results suggest that SsIRF8 might be important in regulating the strength of the rockfish immune response to immunostimulatory agents.

• 한국식품과학회지
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• 제33권3호
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• pp.384-388
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• 2001

오미자의 면역조절작용에 미치는 효과를 살펴본 결과, 오미자(SZX)는 T 및 B세포의 증식을 유의성있게 촉진시켰으며, in vivo 및 in vitro 실험에서 비장내의 T 및 B림프구를 증가시켰고, T세포 중 특히 $T_H$세포를 증가시켰다. 또한 흉선 T림프구 중의 $T_H$세포의 수를 증가시키는 작용을 나타냈다. 아울러 SZX는 in vitro계에서 L1210세포의 apoptosis를 유도하였으며, 복강대식세포에서의 탐식능 및 nitric oxide(NO)생성을 촉진시켰다. 이 결과는 복강대식세포로부터 생성된 NO가 L1210세포의 apoptosis를 유도하는데 중개역할을 하고 있을 가능성을 시사한다. 이상의 결과 오미자는 T, B림프구 및 대식세포 등의 면역세포의 활성을 증강시키는 작용을 보유하고 있으며, 암세포의 apoptosis를 유도하는 기능을 가지고 있음으로써 면역조절제로서의 역할을 가지는 것으로 추정된다.

• 대한미생물학회지
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• 제21권1호
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• Laboraroty Animal Research
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• 제34권4호
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• pp.302-310
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• 2018

CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.