1.Ginsenoside Rg1 and 20(S)-Rg3 Induce IgA Production by Mouse B Cells.
Ha Yan PARK ; Sang Hoon LEE ; Kyu Seon LEE ; Hee Kyung YOON ; Yung Choon YOO ; Junglim LEE ; Jae Eul CHOI ; Pyeung Hyeun KIM ; Seok Rae PARK
Immune Network 2015;15(6):331-336
Ginsenosides are the major components of ginseng, which is known to modulate blood pressure, metabolism, and immune function, and has been used to treat various diseases. It has been reported that ginseng and several ginsenosides have immunoregulatory effects on the innate and T cell-mediated immune response. However, their effects on the humoral immune response have not been fully explored. The present study examined the direct effects of red ginseng extract (RGE) and ginsenosides on mouse B cell proliferation and on antibody production and the expression of germline transcripts (GLT) by mouse B cells in vitro. RGE slightly reduced B cell proliferation, but increased IgA production by LPS-stimulated B cells. Furthermore, ginsenoside Rg1 and 20(S)-Rg3 selectively induced IgA production and expression of GLTalpha transcripts by LPS-stimulated B cells. Collectively, these results suggest that ginsenoside Rg1 and 20(S)-Rg3 can drive the differentiation of B cells into IgA-producing cells through the selective induction of GLTalpha expression.
Animals
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Antibody Formation
;
B-Lymphocytes*
;
Blood Pressure
;
Cell Proliferation
;
Ginsenosides
;
Immunity, Humoral
;
Immunoglobulin A*
;
Metabolism
;
Mice*
;
Panax
2.Effect of Ixeris dentata Nakai Extract on Nitric Oxide Production and Prostaglandin E2 Generation in LPS-stimulated RAW264.7 Cells.
Yu Yeon JUNG ; Jin Tae HONG ; Sang Bae HAN ; Young Hyun PARK ; Dong Ju SON
Immune Network 2015;15(6):325-330
Inflammation is the basis of severe acute and chronic diseases. This study investigated the anti-inflammatory property of a crude methanol extract (MeOH-ex) and the solvent fractions of Ixeris dentata Nakai (IDN) in LPS-stimulated murine macrophage-like cell line RAW264.7. Here, we showed that the ethyl acetate fraction (EtOAc-fr) had the most potent inhibitory activity on LPS-induced nitric oxide (NO) production among the tested samples, i.e., IDN MeOH-ex and the three different solvent fractions (chloroform, n-hexane, and EtOAc). We further found that the EtOAc-fr significantly inhibited LPS-induced prostaglandin PGE2 (PGE2) generation in RAW264.7 cells. Furthermore, the treatment with EtOAc-fr effectively suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). These results suggest that the EtOAc-fr of IDN MeOH-ex exhibits an anti-inflammatory activity in vitro by inhibiting LPS-induced NO production and PGE2 generation via suppression of iNOS and COX-2 expression.
Asteraceae*
;
Cell Line
;
Chronic Disease
;
Cyclooxygenase 2
;
Dinoprostone*
;
Inflammation
;
Methanol
;
Nitric Oxide Synthase
;
Nitric Oxide*
3.Expression of Nucleotide-oligomerization Domain (NOD) and Related Genes in Mouse Tissues Infected with Mycobacterium leprae.
Tae Hoon KIM ; Gue Tae CHAE ; Tae Jin KANG
Immune Network 2015;15(6):319-324
The nucleotide-oligomerization domain (NOD) is an important molecule involved in host defense against bacterial infection. To study the role of NODs in the host response to Mycobacterium leprae, we measured the mRNA levels of NODs and related genes in infected mouse tissues. The mRNA expression of NOD1, NOD2, caspase-1 and ASC was increased in mouse footpads. Whereas NOD2 expression in macrophages was increased at 2 and 24 h post-infection with M. leprae, there was no expression of NOD1 at these time points. An increase in caspase-1 expression was observed at 2 h and continued at 24 h. However, the expression of ASC was increased only at the early time point. The expression of caspase-1 is regulated by NOD2-dependent pathway in established HEK 293. Our results suggest NOD2, rather than NOD1, may be associated with the host response to M. leprae and that caspase-1 activation is essential for the host response.
Animals
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Bacterial Infections
;
Macrophages
;
Mice*
;
Mycobacterium leprae*
;
Mycobacterium*
;
RNA, Messenger
4.Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells.
Immune Network 2015;15(6):313-318
Purification of enough numbers of circulating eosinophils is difficult because eosinophils account for less than 5% peripheral blood leukocytes. Human eosinophilic leukemia EoL-1 cells have been considered an in vitro source of eosinophils as they can differentiate into mature eosinophil-like cells when incubated with dibutyryl cAMP (dbcAMP) or butyric acid. In this study, the viability and phenotypic maturation of EoL-1 cells stimulated by either dbcAMP or butyric acid were comparatively analyzed. After treatment with 100 microM dbcAMP or 0.5 microM butyric acid, EoL-1 cells showed morphological signs of differentiation, although the number of nonviable EoL-1 cells was significantly increased following butyric acid treatment. Stimulation of EoL-1 cells with 0.5 microM butyric acid more effectively induced the expression of mature eosinophil markers than stimulation with dbcAMP. These results suggest that treatment of EoL-1 cells with 0.5 microM butyric acid for limited duration could be an effective strategy for inducing their differentiation. Considering that expression of CCR3 was not sufficient in EoL-1 cells stimulated with 0.5 microM butyric acid, treatment of the chemically stimulated EoL-1 cells with cytokines, which primarily support eosinophil maturation, would help to obtain differentiated EoL-1 cells with greater functional maturity.
Bucladesine
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Butyric Acid*
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Cytokines
;
Eosinophils*
;
Humans*
;
Hypereosinophilic Syndrome*
;
Leukocytes
5.Anti-inflammatory Effect of Alloferon on Ovalbumin-induced Asthma.
Jane JEON ; Yejin KIM ; Hyemin KIM ; Jae Seung KANG ; Wang Jae LEE
Immune Network 2015;15(6):304-312
Asthma is a well-known inflammatory lung disease; however, the specific underlying mechanism is largely unknown. We previously demonstrated that alloferon effectively downregulates pulmonary inflammation. In this study, we examined whether alloferon has a therapeutic effect on asthma. Alloferon remarkably decreased the number of eosinophils, macrophages, and neutrophils in the bronchoalveolar lavage fluid (BALF) from ovalbumin (OVA)-induced asthma mice. It was synergistically decreased with 2.5 mg/kg prednisolone (PDA). Inflammatory cell infiltration around the bronchioles and in the alveolus of OVA-induced asthma mice was effectively prevented by alloferon alone and combined treatment with alloferon and PDS. The production of IL-5 and IL-17 was decreased by alloferon alone and combined treatment with alloferon and PDS. There was no change the level of total immunoglobulin (Ig) following alloferon administration; however, total Ig was decreased by PDS. IgG2a levels were not changed by either alloferon alone or alloferon in combination with PDS. However, the levels of OVA-specific IgG1 and IgE were decreased by alloferon and PDS. In conclusion, our results suggest that a combination of alloferon and prednisolone is effective for the treatment of asthma, as it prevents inflammatory cell infiltration via the down-regulation of IL-5 and IL-17 production and decreases IgG1 and IgE production via the suppression of T helper type 2 immune response.
Animals
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Asthma*
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Bronchioles
;
Bronchoalveolar Lavage Fluid
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Down-Regulation
;
Eosinophils
;
Immunoglobulin E
;
Immunoglobulin G
;
Immunoglobulins
;
Interleukin-17
;
Interleukin-5
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Lung Diseases
;
Macrophages
;
Mice
;
Neutrophils
;
Ovalbumin
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Pneumonia
;
Prednisolone
6.The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.
Jiyea CHOI ; Hyemin KIM ; Yejin KIM ; Mirim JANG ; Jane JEON ; Young Il HWANG ; Won Jun SHON ; Yeong Wook SONG ; Jae Seung KANG ; Wang Jae LEE
Immune Network 2015;15(6):291-303
GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-kappaB activation following ENO1 stimulation.
Arthritis, Rheumatoid
;
Concanavalin A
;
Cytokines
;
Down-Regulation*
;
Humans
;
Inflammation
;
Interleukin-6
;
Interleukins
;
Macrophages
;
Monocytes
;
NF-kappa B
;
p38 Mitogen-Activated Protein Kinases
;
Protein Kinases
;
Telomerase
;
Tumor Necrosis Factor-alpha
7.3,3'-Diindolylmethane Inhibits Flt3L/GM-CSF-induced-bone Marrow-derived CD103+ Dendritic Cell Differentiation Regulating Phosphorylation of STAT3 and STAT5.
Joo Hung PARK ; Ah Jeong CHOI ; Soo Ji KIM ; So Yeon JEONG
Immune Network 2015;15(6):278-290
The intestinal immune system maintains oral tolerance to harmless antigens or nutrients. One mechanism of oral tolerance is mediated by regulatory T cell (Treg)s, of which differentiation is regulated by a subset of dendritic cell (DC)s, primarily CD103+ DCs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating immunity. The intestines are exposed to various AhR ligands, including endogenous metabolites and phytochemicals. It was previously reported that AhR activation induced tolerogenic DCs in mice or in cultures of bone marrow-derived DCs. However, given the variety of tolerogenic DCs, which type of tolerogenic DCs is regulated by AhR remains unknown. In this study, we found that AhR ligand 3,3'-diindolylmethane (DIM) inhibited the development of CD103+ DCs from mouse bone marrow cells stimulated with Flt3L and GM-CSF. DIM interfered with phosphorylation of STAT3 and STAT5 inhibiting the expression of genes, including Id2, E2-2, IDO-1, and Aldh1a2, which are associated with DC differentiation and functions. Finally, DIM suppressed the ability of CD103+ DCs to induce Foxp3+ Tregs.
Animals
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Bone Marrow Cells
;
Dendritic Cells*
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
Immune System
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Intestines
;
Ligands
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Mice
;
Phosphorylation*
;
Phytochemicals
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Receptors, Aryl Hydrocarbon
;
Transcription Factors
8.Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1beta in Dendritic Cells by Regulating NF-kappaB and NLRP3 Inflammasome Activation.
Jae Eun KIM ; Jun Young LEE ; Min Jung KANG ; Yu Jin JEONG ; Jin A CHOI ; Sang Muk OH ; Kyung Bok LEE ; Jong Hwan PARK
Immune Network 2015;15(6):269-277
Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1beta is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1beta production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1beta in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Co-treatment with WA decreased IL-1beta production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1beta and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IkappaB-alpha phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1beta, as well as increased procaspase-1 and pro IL-1beta protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit ac tivation of the NLRP3 inflammasome. NLRP3 activators induced IL-1beta secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1beta and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1beta production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer.
Blotting, Western
;
Caspase 1
;
Dendritic Cells*
;
Down-Regulation
;
Gastritis
;
Gene Expression
;
Helicobacter pylori
;
Helicobacter*
;
Humans
;
Interleukin-1beta
;
Interleukin-6
;
Macrophages
;
NF-kappa B*
;
Peptic Ulcer
;
Phosphorylation
;
Stomach Neoplasms
;
Withania
9.IL-4 Derived from Non-T Cells Induces Basophil- and IL-3-independent Th2 Immune Responses.
Sohee KIM ; Hajime KARASUYAMA ; Angel F LOPEZ ; Wenjun OUYANG ; Xiaoxia LI ; Graham LE GROS ; Booki MIN
Immune Network 2013;13(6):249-256
How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.
Animals
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Basophils
;
Immunization
;
Interleukin-3
;
Interleukin-4*
;
Lymph Nodes
;
Mice
;
Papain
;
Parasites
;
Receptors, Interleukin-3
;
T-Lymphocytes
10.Increased Lymphocyte Infiltration in Rheumatoid Arthritis Is Correlated with an Increase in LTi-like Cells in Synovial Fluid.
Jihye KOO ; Soochan KIM ; Woong Jae JUNG ; Ye Eun LEE ; Gwan Gyu SONG ; Kyung Su KIM ; Mi Yeon KIM
Immune Network 2013;13(6):240-248
In this study, we compared the immune cell populations in rheumatoid arthritis (RA) synovial fluid, which shows lymphoid tissue-like structure, with those in tonsils, which are normal secondary lymphoid tissues. Firstly, we found that CD4-CD11b+ macrophages were the major population in RA synovial fluid and that B cells were the major population in tonsils. In addition, synovial fluid from patients with osteoarthritis, which is a degenerative joint disease, contained CD4+CD11b+ monocytes as the major immune cell population. Secondly, we categorized three groups based on the proportion of macrophages found in RA synovial fluid: (1) the macrophage-high group, which contained more than 80% macrophages; (2) the macrophage-intermediate group, which contained between 40% and 80% macrophages; and (3) the macrophage-low group, which contained less than 40% macrophages. In the macrophage-low group, more lymphoid tissue inducer (LTi)-like cells were detected, and the expression of OX40L and TRANCE in these cells was higher than that in the other groups. In addition, in this group, the suppressive function of regulatory T cells was downregulated. Finally, CXCL13 expression was higher in RA synovial fluid than in tonsils, but CCL21 expression was comparable in synovial fluid from all groups and in tonsils. These data demonstrate that increased lymphocyte infiltration in RA synovial fluid is correlated with an increase in LTi-like cells and the elevation of the chemokine expression.
Arthritis, Rheumatoid*
;
B-Lymphocytes
;
Humans
;
Joint Diseases
;
Lymphocytes*
;
Lymphoid Tissue
;
Macrophages
;
Monocytes
;
Osteoarthritis
;
Palatine Tonsil
;
Synovial Fluid*
;
T-Lymphocytes, Regulatory