• The Journal of Pediatrics of Korean Medicine
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• v.30 no.4
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• pp.29-59
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• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.32 no.3
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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 the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.919-928
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• 2017

The immuno-enhancing effects of alginate oligosaccharides from Sargassum coreanum were investigated. The alginate oligosaccharides were produced by an alginate-degrading enzyme from S. oneidensis PKA 1008. The degraded alginate oligosaccharides were visualized by thin-layer chromatography developed using a solvent system of 1-butanol/methanol/water, 4:1:2 (v/v/v). Alginate was degraded into dimmers at 60 h. As a result, the levels of Th1 cytokine [interferon $(IFN)-{\gamma}$ and interleukin (IL)-2] and Th2 cytokine (IL-6 and IL-10) increased with increasing incubation time compared to the control in vitro. Enzymatic extract treatment promoted proliferation of splenocytes at concentrations of 100 and 200 mg/kg at 24 h in vivo. Secretion of $IFN-{\gamma}$ and IL-2 significantly increased in a dose-dependent manner at 24 h as well as induced higher production of IgG2a in serum. Natural killer cell activity was measured and tended to increase. In addition, complete blood cell counts increased in a dose-dependent manner. These results indicate that alginate oligosaccharides produced by crude enzyme from S. oneidensis PKA 1008 may have significant immune activities.

• The Korea Journal of Herbology
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• v.29 no.4
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• pp.1-8
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• 2014

Objectives : The root bark of Morus alba L. (Mori Cortex Radidus; MCR) has been traditionally used to reduce heat from the lungs, soothe asthma, and edema and to promote urination. In this study, we investigated the effect of MCR ethanol extract on ovalbumin (OVA)-induced allergic asthma in mice. Methods : Mice were sensitized at day 0, 7 and 14 with 0.2% OVA and then airway challenged at day 21, 23, 25, 27 and 29 to induce allergic asthma. MCR extracts at doses of 50 and 100 mg/kg body weight (bw) were orally administered during OVA challenge once per a day. The levels of allergic mediators such as histamine, OVA-specific IgE, IFN-${\gamma}$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed with hematoxylin and eosin (H&E) staining. Results : MCR extract significantly decreased not only the serum levels of histamine, OVA-specific IgE, and IL-4 compared with those of OVA control group, but significantly increased the serum level of IFN-${\gamma}$. In H&E staining, MCR extract inhibited the infiltration of inflammatory cells and bronchiolar damage with epithelial thickening in lung tissues of OVA-induced asthma mice. Conclusions : These results indicate that MCR extract inhibits lung damage by asthma through regulating the allergic immune response, suggesting that MCR may be used as a useful agent for the treatment of allergic asthma.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Journal of Microbiology and Biotechnology
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• v.24 no.12
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• pp.1629-1635
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• 2014

It is known that lactic acid bacteria (LAB) have many beneficial health effects, including anti-oxidative activity and immune regulation. In this study, the immune regulatory effects of Lactobacillus sakei and Lactobacillus plantarum, which are found in different types of kimchi, were evaluated. L. sakei and its lipoteichoic acid (LTA) have greater immune stimulating potential in IL-12, IFN-${\gamma}$, and TNF-${\alpha}$ production as compared with L. plantarum in an in vitro condition. On the other hand, L. plantarum is assumed to repress the Th1 immune response in murine experiments. After being injected with LPS, L. plantarum-fed mice maintained a healthier state, and the level of TNF-${\alpha}$ in their blood was lower than in other bacterial strainfed mice and in the LPS-only control mice. Additionally, IL-12 production was significantly decreased and the production of IL-4 was greatly increased in the splenocytes from L. plantarum-fed mice. Further experiments revealed that the pre-injection of purified LTA from L. plantarum (pLTA), L. sakei (sLTA), and S. aureus (aLTA) decreased TNF-${\alpha}$ and IL-4 production in LPS-injected mice. Mouse IL-12, however, was significantly increased by aLTA pre-injection. In conclusion, the L. sakei and L. plantarum strains have immune regulation effects, but the effects differ in cytokine production and the regulatory effects of the Th1/Th2 immune response.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.179-191
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• 2009

Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naive mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN-${\gamma}$/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.59-74
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• 2010

Objectives : Atopic dermatitis(AD) is a chronic recurrent skin disease which usually developed in infancy or childhood. AD often repeat improvement and relapse. The cause of AD is so indefinite that many methods of therapies(moisturizer, steroid ointment, antihistamine, immunomodulator, immunosuppressant, herbal medicine, alternative medicine, etc.) are tried. Recently, a lot of studies were made. But there is no report about the effect of Samulsopungeum(SM) and Prednisolone(PN) on AD. So, author aimed to investigate the effects of SM and PN on AD of NC/Nga mice. Methods : Thirty two mice(8 Balb/c mice and 24 NC.Nga mice) were divided into four groups; Balb/c mice was normal group. NC/Nga mice were divide into three group : control, PN, SM group. AD was induced in the control, PN, SM group by spreading DNCB. Then normal saline, PN and SM were orally administered three times in a week for 8 weeks to the control, PN, SM group, respectively. We observed changes of clinical skin severity score, serum IgE, IgG1, IFN-$\gamma$, IL-2, IL-4, IL-5, IL-10, IL-13, and so on. We used one-way ANOVA test statistically(p<0.01). Results : The clinical skin severity scores of PN group and SM group in 8th week were decreased compared to the control group. Serum IgE, IgGl levels of PN group and SM group were significantly decreased compared to the control group. Serum IFN-$\gamma$ in SM group was significantly increased compared to the control group. But, Serum IFN-$\gamma$ in PN group was significantly decreased compared to the control group. Serum IL-10 levels of PN group and SM group were significantly decreased compared to the control group. Serum IL-2, IL-4, IL-5, IL-13 levels of PN group and SM group were significantly decreased compared to the control group. mRNA expression levels of IL-2, IL-4, IL-5, IL-13 in the dorsal skin tissues of PN group and SM group were significantly decreased compared to the control group. According to biopsy reports of the ear and skin tissues showed that the tissue damage of PN group and SM group were highly reduced compared to the control group. Creatinine, BUN, ALT, AST levels of PN group and SM group were normal. Conclusion : According to the above results, it is considered that SM is effective treatment for the AD.