• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1517-1526
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• 2016

Lactic acid bacteria (LAB) isolated from fermented foods have potential as a treatment for immune-related disorders and the use of LAB has been increasing worldwide. In this study, the differential cytokine regulatory effect was examined with three isolates of lactobacilli strains; namely, Lactobacillus plantarum K55-5 isolated from dairy product, and L. sakei K101 and L. plantarum K8 previously isolated from kimchi (a Korean traditional fermented vegetable). Production of cytokines such as IL-10, IL-12, IFN-γ, and TNF-α was significantly increased in L. sakei K101- and L. plantarum K55-5-treated splenocytes as compared with controls. The oral administration of L. sakei K101 and L. plantarum K55-5 increased cytokine production in the immunosuppressed mouse splenocytes and blood. NK cell cytotoxic activity was also increased in L. sakei K101- and L. plantarum K55-5-fed mice. On the other hand, L. plantarum K8 did not affect cytokine induction in all the experiments performed in this study. The cytokine-inducing effect of L. plantarum K55-5 was significantly increased by lysates of heat-killed bacteria as compared with live, heat-killed, or supernatant of cell lysates. TNF-α production by lipoteichoic acids (LTAs) isolated from the three isolates of lactobacilli was compared, and it was found that K55-5 LTA had a highest cytokine-inducing ability, which was mediated by TLR2-mediated NF-κB and ERK activation. Taken together, our study suggests that L. plantarum K55-5 and L. sakei K101 can be used for the treatment of immunosuppressed disorders.

• Microbiology and Biotechnology Letters
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• v.39 no.3
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• pp.313-316
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• 2011

We isolated and identified a novel probiotic strain, Lactobacillus sakei proBio65 from Kimchi. To determine whether L. sakei proBio65 has an immunomodulatory effect, we investigated cells via an in vitro screening system which co-cultured freshly isolated mesenteric lymphocyte with probiotics. A significant increase of $Foxp3^+$ transcription regulatory factor expression was observed, followed by an increase in anti-inflammatory cytokines transcription regulatory factor. L. sakei proBio65 exhibited high levels of the IL-10/IL-12 production ratio and enhanced Foxp3 expression in vitro. L. sakei proBio65 may thus be therapeutically useful for the modulation of inflammatory immune disorders.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.119-135
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• 2005

Objectives : The aim of this study was to investigate the Asthma-suppressive and Immune-regulatory effect of AF-HA(Aristolochiae Fructus Herbal-acupuncture) at Joksamni(St36) in OVA(ovalbumin) induced asthma mouse model. Methods : C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). The mice in the OVA-AF-HA group were treated with AF-HA at St36 for the later 8weeks(3times/week). The mice in the OVA-Needle-prick group were treated with single prick with an injection needle at St36 for the later 8 weeks(3times/week). Results : 1. The lung weight and the total cells in lung of the mice treated with AF-HA at St36 decreased significantly compared with those of the OVA-control group. 2. Total leukocytes and eosinophils in BALF of the mice group treated with AF-HA at St36 decreased remarkably compared with those of the OVA-control group. 3. The collagen accumulation in lung of OVA-AF-HA group decreased significantly compared with that of the OVA-control group, 4. The concentrations of IL-4, IL-5, IgE in BALF, and IL-4, IL-5, IL-13 in serum of the mice group treated with AF-HA at St36 decreased significantly compared with those of the OVA-control group. 5. The numbers of $Gr-1^+/CD11b^+\;and\;CD11b^+$ cells in lung of the mice group treated with AF-HA at St36 decreased significantly compared with those of the OVA-control group. 6. The numbers of $CCR3^+,\;CD4^+,\;CD8^+\;and \;CD3e^+/CD69^+$ cells in lung of the mice group treated with AF-HA at 5136 decreased significantly compared with those of the OVA-control group. 7. The mRNA expressions of $TNF-{\alpha}$, IL-4, IL-5, IL13 in lung of the mice group treated with AF-HA at St36 decreased significantly compared with those of the OVA-control group. Conclusion : These results suggest that Aristolochiae Fructus Herbal-acupuncture at Joksamni(St36) may be an effictive therapeutic method to treat asthma.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.46 no.6
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• pp.702-707
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• 2013

Sleep is an essential biological process of which the underlying regulatory mechanisms involve numerous anatomical structures and biochemical substances that can be compromised by stress and the immune system. Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the central nervous system (CNS). It is well established that activation of $GABA_A$ receptors promotes sleep. L. brevis BJ20 fermentation of sea tangle and oysters resulted in stress reduction and sleep inducing effects. This is the first study to report that GABA has the ability to induce sleep related hormones in mice; therefore, it has potential use as a natural sleep aid. These results suggested that sea tangle and oysters fermented by L. brevis BJ20 can be used as potential agents for stress reduction and sleep promotion.

• Natural Product Sciences
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• v.17 no.3
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• pp.239-244
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• 2011

Immediate-type hypersensitivity is involved in many allergic diseases such as asthma, allergic rhinitis and anaphylaxis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells releases inflammatory mediators, such as histamine and pro-inflammatory cytokines with immune regulatory properties. We investigated the effect of the aqueous extract of Schizonepeta tenuifolia (AEST) (Labiatae) on the immediate-type allergic reaction. AEST inhibited compound 48/80-induced systemic allergic reaction. AEST attenuated immunoglobulin E (IgE)-mediated skin allergic reaction and histamine release from human mast cell line (HMC-1) cells. In addition, AEST decreased the gene expression and secretion of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated HMC-1 cells. Our results indicate that AEST inhibits the mast cell-derived allergic reactions and involvement of histamine and pro-inflammatory cytokines in these effects.

• Biomedical Science Letters
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• v.29 no.3
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• pp.137-143
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• 2023

Inflammation plays an important role in immune system's response to tissue injury and biological stimuli. However, excessive inflammation can cause tissue damage. Therefore, the development of naturally derived anti-inflammatory agents have received broad attention. In this study, we investigated the anti-inflammatory mechanism of Rubi Fructus (RF) extract on the mast cell-mediated inflammatory response. To determine the regulatory mechanism of RF in inflammatory reaction, we evaluated the effects of RF on secretion of interleukin (IL)-8, IL-6 and tumor necrosis factor (TNF)-α and activation of nuclear factor-κB (NF-κB) and caspase-1 in activated human mast cells-1 (HMC-1). The results showed that RF attenuated IL-8, IL-6 and TNF-α secretion in a concentration-dependent manner. Moreover, RF significantly attenuated caspase-1and NF-κB activation in activated HMC-1. Conclusively, the present results provide evidence that RF may be a promising agent for anti-inflammatory therapy.

• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5359-5364
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• 2015

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form ;$s\acute{e}ezary$ syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.

• Toxicological Research
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• v.31 no.1
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• pp.11-16
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• 2015

Our body's immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, IL-12, and $IL-1{\beta}$) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-${\beta}$-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.591-598
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• 2021

Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8⁺ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.