• Journal of Periodontal and Implant Science
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• v.50 no.2
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• pp.74-82
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• 2020

Purpose: The aim of this cross-sectional study was to investigate the effect of scaling and root planing (SRP) on the expression of anti-inflammatory cytokines (interleukin [IL]-4, IL-9, IL-10, and IL-13) in the gingival crevicular fluid (GCF) of electronic cigarette users and non-smokers with moderate chronic periodontitis (CP). Methods: Electronic cigarette users and non-smokers with CP were included in the study. Full-mouth plaque and gingival indices, probing depth (PD), clinical attachment loss (CAL), and marginal bone loss (MBL) were assessed. The GCF was collected, and its volume and levels of IL-4, IL-9, IL-10, and IL-13 were assessed. These parameters were evaluated at baseline and 3 months after SRP. The sample size was estimated, and comparisons between groups were performed. P<0.05 was considered to indicate statistical significance. Results: Thirty-six electronic cigarette users (47.7±5.8 years old) and 35 non-smokers (46.5±3.4 years old) with CP were included. At baseline, there were no differences in plaque index (PI), PD, CAL, MBL, and GCF IL-4, IL-9, IL-10, and IL-13 between electronic cigarette users and nonsmokers. At the 3-month follow-up, there were no significant differences in PI, gingival index (GI), PD, CAL, and MBL in electronic cigarette users compared to baseline, while there were significant reductions in PI, GI, and PD among non-smokers. At the 3-month follow-up, GCF IL-4, IL-9, IL-10, and IL-13 levels were significantly elevated in both groups (P<0.05) compared to baseline. The increases in GCF IL-4, IL-9, IL-10, and IL-13 levels were significantly higher in non-smokers (P<0.05) than in electronic cigarette users at the 3-month follow-up. Conclusions: Levels of GCF IL-4, IL-9, IL-10, and IL-13 increased after SRP in electronic cigarette users and non-smokers with CP; however, the anti-inflammatory effect of SRP was more profound in non-smokers than in electronic cigarette users.

• Korean Journal of Pharmacognosy
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• v.43 no.3
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• pp.224-230
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• 2012

Schizandrin (SZ), was isolated from the fruit of Schizandra chinensis, has been reported to have many biological properties, including anti-inflammatory and antitumor activities. However, its anti-allergic effects are not completely elucidated. We focused on the anti-allergic effects of SZ in PMA/ionomycin (PI)-induced rat basophilic leukemia (RBL-2H3) cells and P815 mast cells. Cytokines (IL-4, IL-13), synthesized by basophils and mast cells, are implicated in pathological conditions such as asthma and allergy. The production of IL-4 and IL-13 was quantified by ELISA and the mRNA expression was detected by using RT-PCR assay. In this study, we found that SZ did not show cytotoxic effect at up to 100 ${\mu}M$ on RBL-2H3 cells and mast cells. In addition, SZ inhibited the production of IL-4 and IL-13 and also decreased the level of mRNA in PI-induced RBL-2H3 cells and mast cells in a dose-dependent manner. Thus, we suggest that SZ may have the effect on preventing allergic disorders by inhibiting IL-4 and IL-13 cytokines.

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.4
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• pp.39-66
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• 2015

Objectives The purpose of this study is to investigate the effects of Sesamum indicum extracted (SEI) on atopic dermatitis in an in-vitro and in-vivo experiment using a MC/9 murine mast cells and a NC/Nga mouse. Methods In-vitro experiment, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression were evaluated by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA and manifestations of NFAT-1, NFAT-2, c-jun, c-fos, NF-${\kappa}B$ p65 transcription factors by western blotting. In-vivo experiment, we measured WBC, Eosinophil, Neutrophil, and serum IL-5, IL-13 in NC/Nga atopic dermatitis mouse, IL-5, IL-13, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant by ELISA, the absolute cell numbers of CD4+, CD8+, +Gr-1+CD11b, B220+CD23+ in the axillary lymph node (ALN), peripheral blood mononuclear cells (PBMCs) and dorsal skin tissue, IL-5, IL-13 by Real-time PCR, the distribution of tissue inflammation and cellular infiltration by H&E and toluidine blue. Results SEI decreased IL-4, IL-5, IL-6, IL-13, GM-CSF, TNF-${\alpha}$ mRNA expression, IL-13, MIP-$1{\alpha}$ production and the expression of transcription factors including NFAT-1, c-jun, NF-${\kappa}B$ p65 in MC/9 murine mast cells. SEI orally administration decreased cell number of WBC, Eosinophil, the level of serum IgE, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, B220+CD23+ in the ALN. SEI orally administration also increased absolute cell number of CD8+/CD3+ and decreased Gr-1+/CD11b+ in PBMCs, decreased CD4+ in dorsal skin tissue, inhibited IL-5, IL-13 mRNA expression. Infiltration levels of inflammatory immune cells, mast cells and thickness of epidermis decreased in dorsal skin tissue. Conclusions SEI can regulate allergic inflammatory response suppressed the gene expression and production of cytokines that mediate allergic reactions, and will be able to be effectively utilized in the treatment of atopic dermatitis future.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.4
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• pp.1-29
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• 2014

Objectives Dictamni Radicis Cortex extracts (DRC) has been known to suppress allergic reaction, however the cellular target of DRC and its mode of action remain unclear. The purpose of this study is to investigate the effects of Dictamni Radicis Cortex extracts on DNCB induced atopic dermatitis-like skin lesions of NC/Nga mouse. Methods This study was designed to investigate the effects of DRC extract in the DNP-IgE-induced activation of MC/9 murine mast cell lines in vitro and in the DNCB-induced activation of NC/Nga mouse in vivo. For this investigation, We examined IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA analysis and manifestations of NFAT1, NFAT2, AP-1 and NF-${\kappa}B$ p65 transcription factors by western blotting in vitro. Then, we examined WBC, eosinophil and neutrophil in NC/Nga mouse, IL-5, IL-13 in serum, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $^+Gr-1^+CD11b$, $B220^+CD23^+$ in the ALN, PBMCs and dorsal skin, IL-5, IL-13 in the dorsal skin by Real-time PCR and the distribution of mast cells by H&E and toluidine blue. Results In vitro the mRNA expression of IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$, GM-CSF and IL-13, MIP-$1{\alpha}$ production by ELISA analysis were completely abolished by DRC and the western blot analysis decreased the expression of mast cell-specific transcription factors including NFAT-1, NF-${\kappa}B$ p65. In vivo DRC oral adminstration also decreased the counts of WBC, eosinophils and inflammatory cytokines such as IL-13 and IgE in the serum. DRC oral adminstration elevated IL-4 level in the spleenocyte culture supernatant. DRC oral adminstration decreased total ALN cells, total skin cells, cell numbers of $CD4^+$, $B220^+CD23^+$ in the ALN, $^+Gr-1^+CD11b$ in the PBMCs and $CD4^+$, $CD8^+$ in the dorsal skin. The mRNA expression of IL-5, IL-13, thickness of epidermis, inflammation immune cells and mast cells were abolished by DRC in the dorsal skin. Conclusions Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mouse were much improved by DRC oral adminstration. These results, therefore, suggest that DRC can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mouse, and may play an important role in recovering AD symptoms.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.20-28
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• 2000

The purpose of this research is to investigate the synergistic effect of herb medicines with hydrocortisone and the regulation effect on the immune system of Onbitang and Dangguijakyaksan at the supernatant of PHA-P stimulated PBMC in the patients with minimal change nephrotic syndrome(MCNS). From the measurement of the concentration rate of IL-4, sCD23 and IL-13, the experiment yielded the following results : The Onbitang group showed a greater tendency to suppress IL-4 and IL-13 levels in MCNS group with no statistical significance. It showed very strong suppression in soluble CD23 compared with control group in MCNS group. The Dangguijakyaksan group, though not statistically significant, was inclined to suppress IL-4 level in MCNS group. It shows stronger suppression in sCD23 and IL-13 levels than these of control group in MCNS group. As for the synergistic effect, the group of hydrocortisone with herb medicines(Onbitang or Danguijakyaksan) produced more suppressive effect to IL-13 level in MCNS group than that of hydrocortisone-only group. They also tended to suppress sCD23 and IL-4 levels, though no statistical significance can be given. As to the suppressive effect of 1L-13 level, the group of Onbitang with hydrocortisone showed an increase of 22.6%, while the group of Dangguijakyaksan with hydrocortisone showed 14.7%. So Onbitang is more effective than Dangguijakyaksan. From the above results, a combinative treatment(herb medicines with hydrocortisone) can be an alternative method to substitute for steroid therapy. It can be a more effective therapy than steroid-only therapy because it is expected to reduce side effects and it shows more special effect to suppress IL-13 level. Based on the present results, further investigation concerning the serum IgE elevation is needed.

• The Journal of Pediatrics of Korean Medicine
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• v.26 no.1
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• pp.1-15
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• 2012

$CheongGiGeoYangTang$ has been used for anti-allergenic purpose. However there was no experimental study about its effect. Therefore, this study was designed to investigate the anti-allergenic effect of $CheongGiGeoYangTang$. Methods Modifiability of RBL-2H3 mast cells' IL-4, IL-13 was analyzed by qRT-PCR and ELISA. Also, the suppressive effect of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}B$ p65 transcription factors was observed by western blotting. OVA-specific IgE, IL-4 and IL-13 production in ovalbumin allergy model was examined as well. Results It was showed that the RBL-2H3 mast cells treated with $CheongGiGeoYangTang$ extract(CGGYT) was significantly suppressed mRNA expression, production of IL-4 and IL-13, and prominently inhibited the expression of transcription factors including GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 but not c-Jun. The administration of CGGYT was suppressed the amount of OVA-specific IgE, IL-4 and IL-13 in OVA/alum-sensitized mice. Conclusions We considered CGGYT would regulate the allergic inflammation as inhibition of IL-4 and IL-13 production in activated mast cells and Th2 cells.

• The Journal of Pediatrics of Korean Medicine
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• v.30 no.3
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• pp.1-30
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• 2016

Objectives Previous studies have found out that Forsythiae Fructus (FF) extracts have anti-atopic activities by in vitro experiment. In order to understand more about FF extracts' benefit, we subdivided FF extracts depending on systematic fractionation method by using Methylene chloride (MC), Ethyl acetate (EtOAc), n-BuOH and n-hexane (n-Hx). This study is designed to examine the effect of FF fractions on the PMA- ionomycin-induced activation of RBL-2H3 mast cell lines in vitro and on the DNCB-induced activation of NC/Nga mice in vivo. Methods For this study, we examined IL-4, IL-13 production by ELISA analysis, IL-4, IL-13, IL-31, IL-31RA and TNF-${\alpha}$ mRNA expression by real-time PCR and manifestations of AP-1 and MAPKs transcription factors by western blotting in vitro. Through in vitro experiment, we selected FF n-BuOH fraction that seems the best effective in atopic dermatitis then induced it on NC/Nga mice by DNCB. We measured mice's WBC, eosinophil and neutrophil in heart blood, IL-4, IL-5, IFN-${\gamma}$ in the spleenocyte culture supernatant, the absolute cell numbers of CD4+, CD8+, B220+CD23+, CD3+CD69+ and Gr-1+CD11b+ in the PBMCs, ALN and dorsal skin, IL-5, IL-13, IL-31, IL-31RA in the dorsal skin by real-time PCR and the distribution of immune cells by H&E on dorsal skin and ANL and toluidine blue staining on dorsal skin. Results FF n-BuOH fraction suppressed IL-4, IL-13 production and mRNA expression of IL-4, IL-13, IL-31, IL-31RA and TNF-${\alpha}$. Results from the western blot analysis showed that FF n-BuOH fraction reduced the activation of the mast cell specific transduction factors involved in AP-1 by suppressing JNK and ERK phosphorylation. In the gross, atopic dermatitis induced by DNCB in NC/Nga mice were improved by oral administration of FF n-BuOH fraction. Oral FF n-BuOH fraction also decreased the level of IgE in mice's serum and the level of IL-4 and IL-5 in the spleenocyte culture supernatant, cell numbers of CD8+, B220+CD23+ in the PBMCs, CD4+ in the ALN and CD4+, Gr-1+CD11b+ in the dorsal skin and suppressed mRNA expression of IL-5, IL-13, IL-31, IL-31RA in the dorsal skin. Histological examination showed that infiltration levels of immune cells in atopic dermatitis induced NC/Nga mice were improved by FF n-BuOH fraction. Conclusions FF n-BuOH fraction can reduce pruritus by suppressing IL-31, IL-31RA secretion and modulate molecular mediators and immune cells associated with atopic dermatitis induced in NC/Nga mice which may have played a significant role in recovering atopic dermatitis symptoms.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.33-42
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• 2013

Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

• Journal of Life Science
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• v.13 no.4
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• pp.441-447
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• 2003

To examine the role of protein kinase C (PKC) in regulation of interleukin-1 beta (IL-1$\beta$)-induced iNOS expression, IL-1$\beta$-induced nitrite production was observed in cultured vascular smooth muscle (VSM) cells pretreated with phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-butyrate (PDB) as PKC activator; 4$\alpha$-phorbol-didecanoate (PDD) as PKC non-activator. Nitrite production induced by IL-1$\beta$ was increased by the presence of increasing concentration of PMA ranging from 2 to 200 nM. However, in VSM cells pretreated with PMA and PDB, IL-1$\beta$-induced $NO_2$ production was decreased in proportion to the duration of pretreatment, and most significantly decreased in pretreatment time of 24 hours. Using RT-PCR method, the expression of iNOS mRNA induced by IL-1$\beta$ was decreased in VSM cells pretreated with PMA 200 nM for 24 hours. These results suggest that decrease in IL-I$\beta$-induced nitrite production by the pretreatment of PMA result from inhibition of iNOS expression and the inhibition related to PMA-induced PKC down-regulation.

• ALGAE
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• v.37 no.4
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• pp.331-347
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• 2022

Atopic dermatitis (AD) is one of major skin inflammatory diseases characterized by excessive Th2-mediated immune responses. Recent evidence provides that interlukin-13 (IL-13) plays the role of a key Th2 cytokine that drives the inflammation underlining AD. Due to adverse effects of commercially available synthetic drugs, the need for treatments based on natural products is gaining much attention. Sargassum horneri is an edible brown algae known for beneficial bioactivities including anti-inflammation. We investigated if polyphenol-rich S. horneri extracts (SHE) could suppress AD-like skin lesions in NC/Nga mice and if that involved inhibition of the infiltration of Th2-mediated cytokine IL-13. We observed markedly increased infiltration of IL-13 positive cells in AD-like skin lesions of mice but SHE treatments decreased it. Also, the dermal expression of IL-13 was sufficient to cause inflammatory responses in mice skin resembling human AD. SHE suppressed the dermal infiltration of inflammatory cells where IL-13 plays a crucial role in skin tissues and in the recruitment of inflammatory cells. Furthermore, it was confirmed that SHE reduced T cell, dendritic cell, and macrophage populations in spleen. Moreover, SHE decreased the collagen deposition in skin and ear dermis resulting in reduced fibrosis that occurs in AD due to excessive collagen. Taken together, our results reveal that SHE suppressed the infiltration of inflammatory cells into skin dermis by decreasing the infiltration of IL-13 positive cells. Therefore, SHE could be taken as a useful therapeutic agent to alleviate AD.