• Korean Journal of Acupuncture
• /
• v.35 no.2
• /
• pp.91-97
• /
• 2018

Objectives : This study was performed to investigate immune regulatory effects of the pharmacopuncture with MOK on hyperthyroid rats. Methods : The experimental hyperthyroidism was prepared by the intraperitoneal injection of L-thyroxine(LT4, 0.5 mg/kg) once daily for 2 weeks in Sprague-Dawley(SD) rats. The pharmacopuncture with MOK extract(MOK pharmacopuncture) at doses of 0.3 or 3 mg/kg was injected on acupuncture points in the thyroid glands of hyperthyroid rats once a day for 2 weeks. Propylthiouracil(PTU, 10 mg/kg) as a reference group was subcutaneously injected into the dorsal neck. We measured the levels of $IFN-{\gamma}$ and IL-4 in the sera of rats using enzyme-linked immunosorbant assay(ELISA) and determined the expression of $IFN-{\gamma}$, IL-4, IL-10, and Foxp3 in spleen tissues by reverse transcriptase-polymerase chain reaction(RT-PCR). Results : The treatment of MOK pharmacopuncture in hyperthyroid rats significantly decreased the serum levels of Th1 cytokine, $IFN-{\gamma}$(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU) and significantly increased the levels of Th2 cytokine, IL-4(p<0.05 for MOK 0.3 mg/kg, p<0.001 for MOK 3 mg/kg, and p<0.05 for PTU) compared to control group. Also, the MOK pharmacopuncture significantly increased IL-4 expression(p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU), IL-10(p<0.05 for MOK 3 mg/kg, and p<0.01 for PTU), and Foxp3(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg and p<0.01 for PTU) in spleen tissues of hyperthyroid rats compared to control group. Conclusions : Our results suggest that MOK pharmacopuncture can help to ameliorate the pathological progression of hyperthyroidism by regulation of the Th1/Th2 imbalance.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.18 no.2
• /
• pp.28-35
• /
• 2005

In order to investigate the effects of Gudambopae-Tang on allergic rhinitis, laboratory study about cytokines and OVA-specific IgE was perfomed in the present study. The results are summarized as follow; 1. IL4, IL-5 was increased in medicating group than control group. 2. $IFN-{\gamma}$ was increased in medicating group than control group. 3. total IgE and OVA-specific IgE was significant decreased in medicating group than control group, statistically significant. This study shows experimentally that Gudambopae-tang could reduce allergic reaction in allergic rhinitis. Advanced studies are required to investigate the mechanisms of herbal medicine in allergic rhinitis model.

• IMMUNE NETWORK
• /
• v.3 no.1
• /
• pp.61-68
• /
• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• The Journal of Internal Korean Medicine
• /
• v.30 no.3
• /
• pp.451-464
• /
• 2009

Background and Objective : Cyperus rotundus L. (CR) 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 CR 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-4, IL-5 and IL-10 by ELISA. Results : The results demonstrated that CR 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. CR treatment significantly increased CD4+ T cell population and the IFN-$\gamma$ expression was significantly enhanced, while IL-4 expression was significantly decreased. In addition, in vitro Th1/Th2 polarization experiments revealed that CR enhanced IFN-$\gamma$ secretion in Th1 cells, but reduced the IL-4 in Th2 cells in a dose-dependent manner. Conclusion : These results suggest that CR treatment could be a desirable alternative therapy for the prevention or correction of Th2 dominant pathological disorders, such as allergy and asthma.

• Toxicological Research
• /
• v.34 no.1
• /
• pp.65-73
• /
• 2018

Pretreatment of low-dose lipopolysaccharide (LPS) induces a hyporesponsive state to subsequent secondary challenge with high-dose LPS in innate immune cells, whereas super-low-dose LPS results in augmented expression of pro-inflammatory cytokines. However, little is known about the difference between super-low-dose and low-dose LPS pretreatments on immune cell-mediated inflammatory and hepatic acute-phase responses to secondary LPS. In the present study, RAW 264.7 cells, EL4 cells, and Hepa-1c1c7 cells were pretreated with super-low-dose LPS (SL-LPS: 50 pg/mL) or low-dose LPS (L-LPS: 50 ng/mL) in fresh complete medium once a day for 2~3 days and then cultured in fresh complete medium for 24 hr or 48 hr in the presence or absence of LPS ($1{\sim}10{\mu}g/mL$) or concanavalin A (Con A). SL-LPS pretreatment strongly enhanced the LPS-induced production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, TNF-${\alpha}$/IL-10, prostaglandin E2 ($PGE_2$), and nitric oxide (NO) by RAW 264.7 cells compared to the control, whereas L-LPS increased IL-6 and NO production only. SL-LPS strongly augmented the Con A-induced ratios of interferon (IFN)-${\gamma}$/IL-10 in EL4 cells but decreased the LPS-induced ratios of IFN-${\gamma}$/IL-10 compared to the control, while L-LPS decreased the Con A- and LPS-induced ratios of IFN-${\gamma}$/IL-10. SL-LPS enhanced the LPS-induced production of IL-6 by Hepa1c1c-7 cells compared to the control, while L-LPS increased IL-6 but decreased IL-$1{\beta}$ and C reactive protein (CRP) levels. SL-LPS pretreatment strongly enhanced the LPS-induced production of TNF-${\alpha}$, IL-6, IL-10, $PGE_2$, and NO in RAW 264.7 cells, and the IL-6, IL-$1{\beta}$, and CRP levels in Hepa1c1c-7 cells, as well as the ratios of IFN-${\gamma}$/IL-10 in LPS- and Con A-stimulated EL4 cells compared to L-LPS. These findings suggest that pre-conditioning of SL-LPS may contribute to the mortality to secondary infection in sepsis rather than pre-conditioning of L-LPS.

• Journal of Sasang Constitutional Medicine
• /
• v.12 no.2
• /
• pp.162-170
• /
• 2000

Purpose : Studies on the Regulatory Effect of Cytokine Production in Taumin Patients with Cerebral Infarction by Cheongsimyeonjatang Method : ELISA(enzyme-linked immuno-sorbent assay) Result : Chungsimyeunjatang(CYT) is a prescription for the cerebral infarction (CI) patients of Taeumin according to Sasang constitution philosophy. Taeumin patients with CI were treated with CYT during the acute stage. Clinical signs of CI disappeared markedly in about two to four weeks after oral administration of CYT in all patients. The mean interleukin (IL)-2 plasma levels were slightly lower in the patients with CI than in the normal groups, whereas the mean IL-4, IL-6 and IgE levels were significantly higher in the patients. There were no significant differences in $interferon-{\gamma}$ $(IFN-{\gamma})$ levels between the groups. Serum $IFN-{\gamma}$ and IL-2 levels derived from T helper (Th)1 cells were elevated significantly in the patients with CI by CYT administration. Significant reduced plasma levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with CYT. During the period of CYT administration, there were no other adverse effects. The data indicate that CYT has a good CI treatment effect, and that its action may be due to regulation of cytokine Production.

• IMMUNE NETWORK
• /
• v.15 no.3
• /
• pp.142-149
• /
• 2015

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.

• YAKHAK HOEJI
• /
• v.49 no.1
• /
• pp.25-29
• /
• 2005

This study was performed to investigate the potential of pear (Pyrus pyrifolia) as a immune-modulating functional food by assay of splenocytes proliferation and induction of cytokines (IFN-${\gamma}$, IL-4) in vitro. When mouse splenocytes were exposed to various concentration (0.16, 0.31, 0.63, 1.25, 2.50 mg/ml) of pear methanol extracts (P-M) without mitogens, splenocytes proliferation (SP) was significantly increased. Also, SP to mitogens, concanavalin A (Con A) and lipopolysaccharide (LPS) were significantly increased by P-M when compared with controls. When splenocytes were cultured with P-M in the presence of Con A, cytokine (IFN-${\gamma}$, IL-4) levels in culture supernatant were significantly enhanced in a dose-dependent manner except 2.5 mg/ml when compared with control group. Therefore, our study suggest that the pear has the potential of being an immune-modulating functional food.

• Nutrition Research and Practice
• /
• v.10 no.2
• /
• pp.182-187
• /
• 2016

BACKGROUND/OBJECTIVES: Supplementation with n-3 polyunsaturated fatty acids (PUFAs) has been shown to generally decrease levels of innate immune markers and inflammatory cytokines, but the specific associations between blood levels of PUFAs and those of innate immune markers have not been investigated. Thus, the present study was conducted to test the hypothesis that innate immune markers as well as cytokines are negatively associated with n-3 PUFAs but positively associated with n-6 PUFAs in healthy adults. MATERIALS/METHODS: One hundred sixty-five healthy Korean adults aged 25-70 years old were included in this cross-sectional study. RESULTS: Serum levels of n-3 PUFAs, such as 18:3n3, 20:5n3, 22:5n3, and 22:6n3 were negatively correlated with eosinophil and basophil counts and $TNF-{\alpha}$, $IFN-{\gamma}$, IL-4, and IL-10 levels. Multivariate analysis also showed that serum levels of n-3 PUFAs were negatively associated with monocyte, eosinophil, and basophil counts and $TNF-{\alpha}$, $IFN-{\gamma}$, IL-4, and IL-12 levels. Additionally, the ratio of 20:4n6 to 20:5n3 was positively correlated with eosinophil counts and associated with $TNF-{\alpha}$, $IFN-{\gamma}$, and IL-4 levels. However, NK cell activity was not associated with serum fatty acid composition. CONCLUSIONS: Innate immune markers such as eosinophil, monocyte, and basophil counts were inversely associated with serum levels of n-3 PUFAs, but were positively associated with the 20:4n6/20:5n3 ratio in this population.

• Biomedical Science Letters
• /
• v.20 no.3
• /
• pp.162-167
• /
• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.