• IMMUNE NETWORK
• /
• v.21 no.3
• /
• pp.22.1-22.17
• /
• 2021

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

• Journal of Life Science
• /
• v.23 no.4
• /
• pp.569-577
• /
• 2013

Soy sauce is a traditional fermented seasoning in several oriental countries, such as Korea and Japan, and recently it has been reported to have biological activities. In Korean soy sauce, soybeans and wheat are the two main raw materials. Polysaccharides that originate from the cell wall of soybeans are resistant to enzymatic hydrolysis. These polysaccharides remain in the soy sauce even after fermentation and are termed Kanjang polysaccharides (KPS). In this study, polysaccharides were obtained from dialysate of different soy sauces labeled as A~T and manufactured by fermentation or the acid-hydrolyzate method. We investigated anti-inflammatory activities by examining the effects of these KPS on proinflammatory cytokine release and mRNA expression in mast cells. Histamine and ${\beta}$-hexosaminidase release were strongly decreased by the KPS treatment in RBL-2H3 cells. Treatment with KPS clearly reduced mRNA expression and the release of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-${\alpha}$) in PMACI-stimulated HMC-1 cells. In particular, KPS derived from fermented Kanjang products showed a significant anti-inflammation effect on mast cells compared to the acid-hydrolyzed Kanjang products. This study suggests that KPS appear to be effective in suppressing allergic inflammatory reactions.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.176-176
• /
• 1994

Moraceae comprise a large family of sixty genera and neary 1,400 specieses, including important groups such as Artocarpus, Morus, and Ficus. In particular, Morus(mulberry) is a small genus of tree and shrubs found in temperate and subtropical regions of the Northern hemishere and has been widely cultivated in China and Korea, In addition, the root bark of mulberry tree have been used as an antiphlogic, diuretic, and expectorant in white medicine, and the crude drug is known as "Sangbaikpi" in Korea. Recently, some papers have been published reporting the hypotensive effect, antiviral effect, antifungal effect, inhibitory effect of cAMP-phosphodiesterase, and anticancer effect of this extract. Little is known about that Cortex mori could have been an antiallergic effect. The purpose of this study was the development of an antiallergic agent with an antiallergic effect from Cortex mori. For this, several in vivo and in vitro experimental models were used. Results are 1) Cortex mori inhibited the compound 48/80-induced degranu-lation, histamine release and calcium uptake of rat peritoneal mast cells, 2) compound 48/80-induced anaphylactic shock and cutaneous reaction were significantly inhibited by pretreatment of Cortex mori, and 3) Cortex mori inhibited the ovalbumin-induced late astmatic reaction. From the above results it is suggested that Cortex mori has some substances with an antiallergic activity. Our final purpose of this study is to develope the new drug with an antiallergic activity from Cortex mori

• Journal of Life Science
• /
• v.28 no.3
• /
• pp.293-299
• /
• 2018

Viticis fructus (fruits of Vitex rotundifolia) is the dried fruit from Vitex rotundifolia; is a traditional medicine for treating inflammation, migraines, chronic bronchitis, headaches, eye pain, and gastrointestinal infections; and demonstrates various bioactivities, including anti-allergic, anti-cancer, and anti-inflammatory effects, which are partly due to its phenolic compound content. This study examines the inhibitory effects of viticis fructus (fruits of Vitex rotundifolia) on MMP-2 and MMP-9 expression using gelatin zymography and RT-PCR in phorbol-12-myristate-13-acetate (PMA)-induced HT-1080 fibro-sarcoma cells. Fruits of Vitex rotundifolia were extracted twice using dichloromethane ($CH_2Cl_2$) and methanol (MeOH). The combined crude extracts ($CH_2Cl_2$ and MeOH) significantly inhibited MMP-2 and MMP-9 activities in gelatin zymography. The combined extracts were fractionated into n-hexane, 85% aqueous methanol (85% aq. MeOH), n-butanol, and water, successively according to polarity. Among all solvent-partitioned fractions, 85% aq. MeOH fractions showed the strongest inhibition on the activation of MMP-2 and MMP-9 in gelatin zymography. In PMA-stimulated HT-1080 cells, the expression levels of MMP-2 and MMP-9 mRNA were also greatly inhibited by the 85% aq. MeOH fraction. These results suggest that viticis fructus can be used as an excellent source for anti-invasive agents.

• Herbal Formula Science
• /
• v.5 no.1
• /
• pp.184-202
• /
• 1997

The results of immune response and antiallergic reaction were as follows. 1. Hemagglutinin titer and hemolysin titer were increased in case of AMR, AR, SNH. But the results were not recognized as having significance. 2. PFC was increased in case of AMR, AR. But the results were not recognized as having significance. 3. RFC was increased in all groups, and the results in the AR, SNH were significant. 4. In experimentation of phagocytic activity in peritoneal exudate cells, AR and SNH showed significant increase. In spleen cells AR and SNH showed significant increase. In monolymphocytus cells AMR, AR and SNH were increased, but result of AMR was of no significance. 5. I examined promotion on spleen cells transformation. As these results, AMR showed increase in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ in comparison with control group. And in $500{\mu}g/m{\ell}$ AMR showed increase in case of 24 hours, 72 hours incubation, but showed decrease in case of 48 hours incubation. AR showed increase in all. In $50{\mu}g/m{\ell}$ SNH showed increase in comparison with control group. And in $500{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ SNH showed increase in case of 24 hours, 48 hours incubation, but showed decrease in case of 72 hours incubation. 6. I examined proliferation of spleen cells. As these results AMR and SNH showed the highest increase in $50{\mu}g/m{\ell}$, but showed the lowest increase in $5000{\mu}g/m{\ell}$. AR showed the highest increase in $500{\mu}g/m{\ell}$, but this result was the almost same in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$. And AMR, AR, SNH showed higher activity in Lipopolysaccharide than Concanavalin A. 7. In all groups results of PCA were decreased in 2 week. In 4 week AR and SNH showed decrease, but AMR didn't show change. In 6 week AR and SNH showed decrease, but on the contrary AMR showed increase. 8. In experimentation on histamine contents, AMR showed significant increase at first agent contact. And AR, SNH showed decrease at first agent contact, but these results were of no importance. At second agent contact AMR showed decrease, but was of no importance. AR, SNH showed significant decrease. At third agent contact, AMR showed significant increase. AR, SNH showed decrease, but these results were of no importance. From above these results, AR and SNH showed good effects on immunoreaction. And all the herb medicines in this examination showed good effects in promotion on spleen cells transformation and proliferation of spleen cells, especially activated B-cells. AR, SNH showed good effects on anti-allergic reaction, but AMR was almost inefficient. Accordingly I think that AR shall be used in disease bringing about a lowering of immunity, that is, AR shall be used in strengthening the body resistance. And I think that SNH shall be used in eliminating pathogenic factors with strengthening the body resistance. It is necessary to a deep study in future.

• Journal of Haehwa Medicine
• /
• v.16 no.2
• /
• pp.147-169
• /
• 2007

To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.

• Journal of Life Science
• /
• v.21 no.10
• /
• pp.1364-1369
• /
• 2011

Mast cells, the central effector cells involved in the allergic response, release histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of the ethyl acetate fraction (EA), derived from Korean rice wine lees, on RBL-2H3 cell degranulation and passive cutaneous anaphylaxis in an animal model. The EA fraction suppressed the release of beta-hexosaminidase, a marker of degranulation, and the mRNA expression of interleukin-3 (IL-3) and IL-13. EA also successfully suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that EA can inhibit mast cell degranulation through the inhibition of IL-3 and IL-13 mRNA expression, and that EA may potentially serve as an anti-allergic agent.

• Journal of Life Science
• /
• v.27 no.10
• /
• pp.1130-1136
• /
• 2017

Traditionally, the larvae of Allomyrina dichotoma (AD), a species of the rhinoceros beetle, have been widely used for their antidiabetic, antihepatofibrotic, antineoplastic, and antiobesity effects. The United Nations' Food and Agriculture Organization has reported on the possibility of using edible insects in human dietary supplements in the future. However, despite the growing interest in insect-based bio-active products, the biological activities of these products have rarely been studied. Previously, we reported that AD larvae inhibit the in vitro differentiation of adipocytes via transcription factor downregulation. In this study, our objective was to evaluate the effects of a hot-water extract of AD larvae on allergy and inflammation. To investigate the inhibitory effect of the extract on allergic reactions, we measured the levels of ${\beta}-hexosaminidase$, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-4 (IL-4), and cyclooxygenase-2 (COX-2) after activation of RBL-2H3 cells using Compound 48/80. In addition, the inhibitory effect of the extract on inflammation was determined using Raw 264.7 cells after lipopolysaccharide (LPS) stimulation. The extract significantly inhibited the ${\beta}-hexosaminidase$, $TNF-{\alpha}$, IL-4, and COX-2 levels in RBL-2H3 cells. Furthermore, it effectively inhibited the inflammatory cytokine IL-6, nitric oxide, and inducible nitric oxide synthase expression in LPS-stimulated Raw 264.7 cells. These results suggest that AD larval extract can be potentially developed as an antiallergic and anti-inflammatory therapeutic agent.

• Journal of Microbiology and Biotechnology
• /
• v.19 no.2
• /
• pp.155-160
• /
• 2009

Mast cells and basophils perform important functions as pivotal effector cells in IgE-mediated allergic reactions. KU812F cells, a human basophilic cell line isolated originally from chronic myelocytic leukemia, express a high affinity receptor of IgE, $Fc{\varepsilon}RI$. Kaempferol was extracted and isolated from a methanolic extract of flavonoid-rich Nelumbo nucifera stamens. In the present study, the inhibitory effects of kaempferol on $Fc{\varepsilon}RI$ expression in human basophilic KU812F cells was examined. Flow cytometric analysis revealed that $Fc{\varepsilon}RI$ expression on the cell surface was suppressed in a concentration-dependent manner when the cells were cultured with kaempferol. Moreover, RT-PCR analysis showed that the mRNA levels for $Fc{\varepsilon}RI$ ${\alpha}-\;and\;{\gamma}$-chains were reduced as the result of kaempferol treatment in a concentration-dependent manner. Kaempferol showed its suppressive effects on intracellular $Ca^{2+}$ concentration and histamine release from anti-$Fc{\varepsilon}RI$ ${\alpha}$-chain antibody-stimulated cells in a concentration-dependent manner. These observations indicate that kaempferol may exert antiallergic effect via down regulation of $Fc{\varepsilon}RI$ expression and degranulation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.4 no.1
• /
• pp.23-42
• /
• 1991

This study were done to know the effects of Dangkiyeumja on the in vivo and in vitro immune responses of mice. The recipes of Dangkiyeumja used in this study enhanced such, cellular functions of immunocytes as phagocytic capacity of macrophages, rossett-eforming abilities of splenocytes and metabolic activities of lymphocytes, However, the same recipes decreased the formation of such reactive oxygen intermediates(ROI) as superoxide and hydrogenperoxide from the macrophages. The effects of the same recipes on the in vim immune responses was suppressive on the cellular immune response(CIR)measured by delayed-type hypersensitivity against dinitrofluorobenzene and mildly enhancing for the humoral immune response measured by antibody production against sheep red blood cells. The results of this study could be summarized as follow: 1. Administration of Dangkiyeumja enhanced the phagocytic activity of the murine macrophage. 2. Administration of Dangkiyeumja decreased the formation of ROI in the murine macrophage 3. Administration of Dangkiyeumja increased the number of the splenic rotte forming cells in the mouse. 4. Administration of DangKiyeumja did not effect the antibody production against sheep red blood cells. 5. Administration of Dangkiyeumja depressed the delayed-type hypersenitivity against dinitrofluoro benzene in the mouse. The result of this study suggest that Dangkiyeumja could ameliorate the hypersensitivity reactions by reducing the formation of ROI and decreasing the CIR without affecting the other functions of immunocytes.