• Asian-Australasian Journal of Animal Sciences
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• v.13 no.10
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• pp.1414-1421
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• 2000

Sixteen specific pathogen free 4-wk-old crossbred weanling pigs were allotted into a $2{\times}2$ factorial experiment to evaluate the effects of chromium (Cr) on the immune responses after lipopolysaccharide (LPS) injection. Two factors included (1) no Cr or 400 ppb Cr supplementation from chromium picolinate (CrPic) and (2) LPS injection ($200{\mu}g/kg$ BW, intraperitoneally) on day 21 (d 21) and 35 (d 35) as compared with saline application. Plasma samples were obtained from all piglets before (0 h) and at 2 h, 4 h, 8 h, and 24 h after LPS injection. The changes in tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and leukocyte populations after LPS injection were not significant on d 21. On d 35, the plasma $TNF-{\alpha}$ level was increased at h 2 postinjection, and supplemental Cr reduced the $TNF-{\alpha}$ level. The leukocyte populations had changed profoundly and lymphocyte subsets of $CD2^+$ and $CD8^+$ were reduced at 8 h postinjection. The blood granulocytes were increased and the percentage of $CD2^+$ was reduced in the Cr-fed group on d 35. Furthermore, Cr supplementation decreased the blastogensis of concanavalin A-stimulated peripheral blood mononuclear cells (PBMC) on d 21. These results suggest that 400 ppb Cr supplementation from CrPic in diets may modulate the immune responses in weanling pigs during LPS injection.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.154-165
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• 2021

This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.23-31
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• 1982

1) Experiments were undertaken to elucidate the mechanism which elevates the systemic arterial blood pressure by cadmium (Cd). 2) The mean arterial pressure and peripheral resistance of central ear artery in Cd-poisoned rabbit were significantly increased in comparison with those in control. 3) The vascular pressure response to electrical stimulation in Cd-poisoned group was less than that in control. However, in the former group it showed the supersensitivity to norepinephrine. 4) The response to electrical stimulation was diminished by sodium arachidonate in the ear artery, on the contrary, it was rather enhanced in the vessel of Cd-poisoned group. The responses in both groups were reduced by pretreatment with either $PGE_2\;or\;PGF_{2{\alpha}}$. 5) The response to electrical stimulation was not affected in control, but enhanced in Cd-poisoned group by pretreatment with indomethacin. 6) When the ear artery of control group was perfused with physiological salt solution (PSS) the response to electrical stimulation was not changed by indomethacin, it was much enhanced without affecting on the response to norepinephrine when $K^+-free\;PSS$, was used. These results demonstrate the evidence that the alteration of regulatory mechanism on the vessels was causally related to the elevation of arterial pressure and the increase in peripheral resistance in Cd-poisoned rabbits.

• 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.

• Journal of Soil and Groundwater Environment
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• v.11 no.1
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• pp.14-22
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• 2006

Laboratory column experiment for simultaneous removal of Cd and Cr(VI) were conducted using newly developed material of Fe-loaded zeolite having both reduction ability and sorption capacity. The solution containing Cd and Cr(VI) was injected into the column and the breakthrough curves (BTCs) for the contaminants were observed at the effluent port. Cd breakthrough was not initialized until Cr(VI) breakthrough was completed. Therefore it could be concluded that overall efficiency of Fe-loaded zeolite should be determined by the reactivity for Cr(VI). The relative concentration of Cr(VI) BTC increased to the unit value while initial breakthrough was delayed and the propagation of breakthrough was slowed. In order to quantitatively describe the shape of Cr(VI) BTC, new parameters of ${\alpha}\;and\;{\beta}$ designated to be shape parameters, were defined and applied in contaminant transport concentration. These parameters were employed to represent the degree of initial breakthrough delay and the degree of breakthrough propagation, respectively. As initial contaminant concentration increased, ${\alpha}$ decreased, which indicated the delay of BTC's initiation. And as initial contaminant flow rate increased, ${\beta}$ decreased, which represented the faster propagation of the BTC. From these results, Fe-loaded zeolite was found to be an effective reactive material for PRBs against heavy metals having different ionic forms in groundwater. And it could be expected that as groundwater flows faster, the propagation of breakthrough would be faster and as contaminant concentration is higher, the initial point of breakthrough would appear earlier.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.279-288
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• 1996

Chronic exposure to cadmium impairs various renal tubular functions, including organic acid (anion) secretion. To investigate the mechanism of cadmium-induced alterations in the organic anion transport system, kinetics of p-aminohippurate (PAH) uptake was studied in renal cortical basolateral membrane vesicles (BLMV) isolated from cadmium-intoxicated rats (adult male Sprague-Dawley). Cadmium intoxication was induced by subcutaneous injections of $CdCl_{2}$ (2 mg Cd/kg per day) for 3 weeks. The renal plasma membrane vesicles were prepared by Percoll gradient centrifugation. The vesicular uptake of $^{14}C$-PAH was determined by rapid filtration technique using Millipore filter. Cadmium intoxication resulted in a marked attenuation of $Na^{+}$-dependent, ${\alpha}$-ketoglutarate (${\alpha}$KG)-driven PAH uptake with no changes in $Na^{+}$ and ${\alpha}$KG-independent transport component. Kinetic analysis indicated that Vmax, but not Km, of the $Na^{+}$-dependent, ${\alpha}$KG-driven component was reduced. A similar reduction of $Na^{+}$-dependent, ${\alpha}$KG-driven PAH uptake was observed in normal membrane vesicles directly exposed to inorganic cadmium in vitro, and this was accompanied by an inhibition of both $Na^{+}$-dependent ${\alpha}$KG uptake and ${\alpha}$KG-PAH exchange activity. These results indicate that during chronic exposure to cadmium, free cadmium ions liberated in the proximal tubular cytoplasm directly interact with the basolateral membrane and impair the active transport capacity for organic anions, most likely due to an inhibition of both $Na^{+}$-dicarboxylate cotransporter and dicarboxylate-organic anion antiporter activities.

• The Korea Journal of Herbology
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• v.25 no.1
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• pp.55-63
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• 2010

Objectives : The object of this study was to verify the inhibitory effect of a decoction of Eucommiae ulmides OLIVER (EU) and Dipsacus asperoides C. Y. Cheng et T.M.Ai (DA) on Collagen II-induced Arthritis Mice (CIA mice). Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. Boostnig same collagen 21 days later, arthritis was induced and then administrated orally the extract of EU+DA (200 or 50 mg/kg) once a day for 4 weeks and compared with that of methotrexate (MTX, 0.3 mg/kg) as a positive control. Results : Administration of EU+DA suppressed the inflammatory progression of CIA mice and the results were 1. Arthritis index of CIA mice was decreased. 2. EU+DA decreased the production of TNF-$\alpha$, IL-6, IL-$1{\beta}$ in the serum of CIA mice. 3. EU+DA decreased the level of IgM. 4. EU+DAincreasaed $CD3^+$, $CD4^+$, $CD4^+$/CD25 but decreased $CD19^+$, $CD3^+/CD49b^+$(NKT), $CD3^-/CD49b^+$(NK), $B220^+/CD23^+$ in PBMC of CIA mice. 5. EU+DA decreased $CD3^+$, $CD4^+$, $CD3^+/CD69^+$ of paw joint in CIA mice. 6. EU+DA decreased subsynovial inflammation. Conclusions : This results demonstrated that extract of EU+DA suppressed the inflammatory progression of CIA mice and supported further studies are required to clarify a mechanism of therapeutic role.

• The Korean Journal of Food And Nutrition
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• v.32 no.5
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• pp.408-416
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• 2019

This study investigated the anti-inflammatory effects of processed (Beopje) curly dock (Rumex crispus L.) in LPS (lipopolysaccharide)-stimulated murine RAW 264.7 cells. The experimental group was classified into five groups : LPS no treatment, CD (curly dock), CD-B (CD processed through Beopje), LPS, LPS+CD-B (LPS+CD processed through Beopje) and LPS+CD (LPS+CD). Treatment of the Raw 264.7 cell lines using LPS led to a significant increase in NO production, pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$), and inflammation related genes (COX-2 and iNOS). Investigation of the inhibitory effects of CD and processed CD on NO production and expression of iNOS and COX-2 was done in LPS-induced RAW 264.7 cells. There was significant inhibition of NO production by LPS+CD and LPS+CD-B in a dose-dependent manner (p<0.05). Particularly, LPS+CD-B exhibited reduced mRNA expression of iNOS and COX-2 and NO production as compared to LPS+CD in Raw 264.7 cell lines (p<0.05). These results may explain some known biological activities of curly dock including the anti-inflammatory effects. CD-B in particular exhibited the highest anti-inflammatory effects of inhibiting production of NO, through the regulation of inflammatory related genes and pro-inflammatory cytokines. These results of Beopje processing might help decrease the anti-biological effects and increase several active substances of curly dock.

• Journal of Microbiology and Biotechnology
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• v.17 no.7
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• pp.1169-1176
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• 2007

Genes encoding proteins responsible for limonene catabolism were cloned from a limonene-degrading microorganism, Enterobacter cowanii 6L, which was isolated from citron (Citrus junos) peel. The 8.6, 4.7, and 7.7 kb fragments (CD3, CD4, and CD6) of E. cowanii 6L chromosomal DNA that confer to E. coli the ability to grow on limonene have been cloned and their corresponding DNA sequences were determined. Nine open reading frames (ORFs) were identified, and the four ORFs (921 bp of CD3-2; 1,515 bp of CD4-1; 1,776 bp of CD6-1; and 1,356 bp of CD6-2) that encode limonene hydroxylase were confirmed by independently expressing these genes in E. coli. FAD and NADH were found to stimulate the hydroxylation reaction if added to cell extracts from E. coli recombinants, and multiple compounds (linalool, dihydrolinalool, perillyl alcohol, (${\alpha}-terpineol$, and ${\gamma}-terpineol$) were the principal products observed. Our results suggest that the isolate E. cowanii 6L has a broad metabolic capability including utilization of limonene. This broad metabolic ability was confirmed by identifying four novel limonene hydroxylase functional ORFs in E. cowanii 6L.