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

• Journal of Acupuncture Research
• /
• v.22 no.6
• /
• pp.61-74
• /
• 2005

Objectives : The aim of this study was to investigate the effect of Asthma-depression and Immunoregulation with PR-HAS(Herbal-acupuncture with Platycodi Radix infusion solution) injection at Joksamni(St36) on ovalbumin-induced asthma in mice. Methods : C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). The experimental group(OVA-PR-HA) wase treated with concentrations(1%) of PR-HAS at Joksamni(St36) for the later 8 weeks(3times/week). The second experimental group(OVA-Needle prick) was treated with Needle-Prick at Joksamni(St36) for the later 8 weeks(3times/week). Results : 1. The weight and total cells in the mice lung treated with PR-HA decreased significantly compared with that of control group. 2. Total leukocytes and eosinophils in BALF of the mice group treated with PR-HA decreased remarkably compared with those of control group. 3. The sticking of collagen on histological analysis of lung sections, the mice group treated with PR-HA decreased significantly compared with those of 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 PR-HA decreased significantly compared with those of control group. 5. The number of $Gr-1^+/CD11b^+\;and\;CD11b^+$ cells in the lungs of the mice group treated with PR-HA decreased significantly compared with that of control group. 6. The numbers of $CCR3^+\;cells,\;CD4^+\;cells\;and\;CD8^+\;cells$ in the lungs, and $CD3e^+/CD69^+$ in the lungs of the mice group treated with PR-HA decreased significantly compared with those of control group. 7. The mRNA expression of ${\beta}-actin,\;TNF-{\alpha}$, IL-4, IL-5,IL-13 in the mice group treated with PR-HA with RT-PCR decreased significantly compared with those of control group. Conclusion : 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 PR-HA decreased significantly compared with those of control group. The number of $Gr-1^+/CD11b^+\;and\;CD11b^+$ cells in the lungs of the mice group treated with PR-HA decreased significantly compared with that of control group. The numbers of $CCR3^+\;cells,\;CD4^+\;cells\;and\;CD8^+\;cells$ in the lungs, and $CD3e^+/CD69^+$ in the lungs of the mice group treated with PR-HA decreased significantly compared with those of control group. The mRNA expression of ${\beta}-actin,\;TNF-{\alpha}$, IL-4, IL-5, IL-13 in the mice group treated with PR-HA with RT-PCR decreased significantly compared with those of control group. These result suggests that Platycodi Radix Herbal-acupuncture at Joksamni(St36) in C57BL/6mice may be an effictive part to OVA-induced asthma in C57BL/6 mice.

• The Journal of Internal Korean Medicine
• /
• v.28 no.4
• /
• pp.681-693
• /
• 2007

Background and Objective : Atractylodes japonica (AJ) is a commonly-used herbal medicine in Asian countries such as Korea, China and Japan. The present study was designated to evaluate the direct effects of AJ on helper T cell activities and on Th1/Th2 lineage development in vitro. Materials and Methods : Spleen cells from 8-week BALB/c mice were cultured in CR extracts containing medium without activation for 24 hours and with activation for 48 hours. CD4+ T cells were isolated and analyzed for mRNA expression levels of INF-$\gamma$, IL-4, T-bet and GATA-3 by RT-PCR and secretion cytokines levels of INF-$\gamma$, IL-2, IL-4, IL-5 and IL-10 by ELISA. Results : The results demonstrated that AJ had no mitogenic effects on unstimulated CD4+ T cells, but augmented CD4+T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. AJ treatment significantly increased CD4+ T cell population and IFN-$\gamma$ expression was significantly enhanced, while IL-4 expression significantly decreased. In addition, in vitro Th1/Th2 polarization experiments revealed that AJ enhanced IFN-$\gamma$ secretion in Th1 cells, but reduced the IL-4 in Th2 cells in dose-dependent manner. Conclusion : These results suggest that AJ treatment could be a desirable alternative therapy for the prevention or correction of Th2 dominant pathological disorders, such as allergy and asthma.

• BMB Reports
• /
• v.34 no.6
• /
• pp.578-583
• /
• 2001

As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

• Archives of Pharmacal Research
• /
• v.21 no.5
• /
• pp.537-542
• /
• 1998

to more effectively drive immune responses toward antigen-specific T helper type 2 (Th2) cell-mediated responses, we constructed a mammalian expression vetor (oPVA/IL4) carrying a fused gene in which the ovalbumin (OVA) cDNA was covalently linked to murine interleukin-4 (IL-4) cDNA. A biologically active OVA/IL4 DNA, as demonstrated by Wes tern blotting and cytokine bioassay. In tramuscular injection of BALB/c mice with the pOVA/IL4 DNA increased both the production of OVA-specific IL-4 by CD$4^{+}$ T cells and the ratio of anti-OVA lgG1 to anti-OVA lgG2a isotypes, while the injection with the pOVA DNA alone, or with the mixture of the pOVA and pIL4 DNA did no or little increase. furthermore, the OVA-specific, Th2 cell-mediated immune responses were significantly enhanced by multiple injections with the pOVA/IL4 DNA. These studies indicate that the direct linkage of an OVA gene to an IL-4 gene in the expression plasmid confines the effects of IL-4 to the OVA-specific cells, efficiently driving the immune response toward OVA-specific, Th2 cell-mediated responses.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.8
• /
• pp.1109-1114
• /
• 2021

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

• IMMUNE NETWORK
• /
• v.10 no.1
• /
• pp.1-4
• /
• 2010

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing $CD4^+$ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.

• Journal of Embryo Transfer
• /
• v.21 no.4
• /
• pp.281-286
• /
• 2006

This study was conducted to investigate the hormonal changes in cultured medium during in vitro culture of bovine oviduct epithelial cells (BOEC) supplemented with interleukin (IL)-4 of 0.001, 0.01, 0.1 or 1 ng/ml. BOEC were collected from the oviduct and washed 3 times with 1% antibiotic-mycotic-DMEM medium and cultured at $39^{\circ}C$, 5% $CO_2$, 95% air for 24$\sim$120 hrs. The cultured media were analyzed hormonal changes with hormonal analyzing kit (progesterone (P4), estradiol (E2) : Perkin Elmer, USA) and Transforming growth factor (TGF)-$\beta$ with Eliza kit (Promega, USA). The production of P4 in 0.001 IL-4 was increased as the culture time increased. P4 production was significantly higher in the medium cultured for 120 hrs than 24 hrs (P<0.05). P4 production in 0.01 ng/ml group was similar to that of 0.001 ng/ml. The production of E2 in 0.001 and 0.01 ng/ml groups were increased to 72 hrs like P4 production and showed significantly different between the culture periods (P<0.05). After the culture for 96 hrs, P4 and E2 production were increased to 96 hrs, but decreased at 120 hrs. The production of TGF-$\beta$ showed no changes according to culture period or supplementation of IL-4. In conclusion, the supplementation of IL-4 can increase the production of P4 and E2 and might have important role for the successful pregnancy in bovine.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.28 no.4
• /
• pp.74-91
• /
• 2015

Background and Objective : Asthma is a chronic inflammatory disease at the mucosa and is associated with excess production of Th2 cytokine and eosinophil accumulation in lung.Gamchomahwang-tangextract(GME) is one of the well known prescription used in oriental medicine for treating asthma. This study was designed to compare the anti-asthmatic effect of GME according to the ratio of 2 compounds.Methods : To examine the effects of GME on asthma, mice were sensitized with 100 ㎍ of OVA and 1 ㎎ of aluminum potassium sulfate(Alum; Sigma) intraperitoneally on day 1 and 15. From day 22, mice were challenged on 3 consecutive days with 5% OVA. The anti-asthmatic effects of GME were evaluated by enhanced pause(Penh), bronchoalveolar lavage fluids (BALF), inflammatory cytokine production and genes expression, serum IgE production. and histological change in lung tissue. GMEⅠ consists of ES and GU in the proportion 2:1(300 ㎎/㎏ group), GMEⅡ consist of ES and GU in the proprtion 4:1(300 ㎎/㎏ group).Results : GMEⅠ,Ⅱ generally inhibited lung inflammation, inflammatory cells infiltration and cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and serum IgE level. GMEⅡ significantly reduced the cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and GMEⅠ decreased cytokine production of IL-4, IL-13 in BALF and gene expression of IL-4, IL-5 in Lung. GMEⅡ potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR(airway hyper-reactivity). Overall the results show that GMEⅡ has more effect on inhibiting production, gene expression of cytokine, serum IgE level and development of Penh than GMEⅠ. Consequently, GMEⅡ might be more effective than GMEⅠ at inhibiting allergic asthma on the OVA-induced mice model.Conclusion : These results indicate that GME has a deep inhibitory effects on airway inflammation and hyperresponsiveness in mice model of asthma and that suppression of IL-4, IL-5, IL-13 expression and decrease of IL-4, IL-5, IL-13 production in BALF might contribute this effect. Hence, the results indicate that GME might be useful herbal medicine of allergic asthma. As a result, GMEⅡ mght be superior to GMEⅠ in the aspect of anti-asthmatic effect on the OVA-induced mice model.

• Herbal Formula Science
• /
• v.16 no.1
• /
• pp.185-205
• /
• 2008

The purpose of this study is to determine whether the clinical activity of patients with atopic dermatitis(AD) correlate with their serum cytokine levels. 86 patients with AD were treated with KHS, YMH and GHT. On each visit to the clinic, their skin status was evaluated using the SCORAD index and serum IL-4, $IFN-{\gamma}$, IL-12, IL-13, IL-2 and IL-10 were measured by ELISA. After oral administration of herbal medicine, patients' skin status and subjective parameters such as pruritus and sleeplessness were significantly improved according to regression analysis. In particular, patients aged 0-9 showed stronger responses to treatment, which implies that the younger patients aged, the easier the treatment by herbal formula became. In analysis of the type of chosen herbal medicines, YMH treated group showed a stronger response in reduction of affected lesion, intensity of a lesion and subjective symptoms, while KHS treated group showed the least reduction. The levels of serum IL-4, $IFN-{\gamma}$ and IL-2 correlated with disease activity. Moreover, in patients under 0-9, the IL-4 level had a corrleation with disease activity; patients under 10-19 showed a correlation between the levels of IL-4 and IL-2 and disease activity; patients under 20-29 showed a correlation between the levels of IL-2, IL-12 and $IFN-{\gamma}$ and disease activity. In comparison with chosen herbal medicines, the groups treated with YMH or GHT treated group showed a correlation between the levels of IL-4, IL-12 and IL-2 and disease activity while KHS treated group did not. Our data suggest that serum levels of IL-4 and IL-13 are good indicators of clinical improvement in treating AD.