• Archives of Pharmacal Research
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• v.29 no.4
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• pp.302-309
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• 2006

Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-${\alpha}$, IL-6, IL-10 and IFN-${\gamma}$, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 hand 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-${\gamma}$ and bronchoalveolar lavage (BAL) IL-6 and IFN-${\gamma}$ were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-${\alpha}$ were not. And levels of BAL TNF-${\alpha}$, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-${\alpha}$, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-${\alpha}$, IL-6, and IL-10 in lupuslike chronic inflammation syndrome compared with normal condition.

• BMB Reports
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• v.54 no.10
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• pp.534-539
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• 2021

IL-10⁺ regulatory B (Breg) cells play a vital role in regulating the immune responses in experimental autoimmune encephalomyelitis, colitis, and contact hypersensitivity (CHS). Several stimulants such as lipopolysaccharide (LPS), CD40 ligand, and IL-21 spur the activation and maturation of IL-10⁺ Breg cells, while the epigenetic mechanism for the IL-10 expression remains largely unknown. It is well accepted that the histone acetylation/deacetylation is an important mechanism that regulates the expression of IL-10. We found that entinostat, an HDAC inhibitor, stimulated the induction of IL-10⁺ Breg cells by LPS in vitro and the formation of IL-10⁺ Breg cells to suppress CHS in vivo. We further demonstrated that entinostat inhibited HDAC1 from binding to the proximal region of the IL-10 expression promoter in splenic B cells, followed by an increase in the binding of NF-κB p65, eventually enhancing the expression of IL-10 in Breg cells.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.182-190
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• 2006

Objective : Based on immunological mechanisms, this study examined whether subcutaneous (s.c.) injection of Clematis mandshurica Maxim. water extract (CMA) has anti-inflammatory effects, and its effect on $TNF-{\alpha}$, IL-1 and IL-10 release from synoviocytes on adjuvant arthritis (AA) in the rat. Methods : Complete Freund's adjuvant was used to induce AA in rats. Synoviocytes were separated by the method of collagenase and DNase digestion Synoviocytes proliferation was assayed by 3-(4, 5 dimethylthiazol 2 yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. $TNF-{\alpha}$, IL-1 and interleukin-10 (IL-10) production of synoviocytes was measured with ELISA. The expression of IL-10 mRNA of synoviocytes was determined using RT PCR. Results : There were significant secondary inflammatory reactions in AA rats, accompanied by the decrease of body and immune organs weight simultaneously. Synoviocytes proliferation of AA rats significantly increased, and the levels of $TNF-{\alpha}$ and IL-1 in supernatants of synoviocytes in AA rats were also elevated compared with the sham group. The administration of CMA (2, 5, 10 mg/kg, s.c.) reduced the above changes significantly. In contrast to $TNF-{\alpha}$ and IL-1, IL-10 production and the level of its mRNA of synoviocytes in AA rats apparently decreased. CMA (2, 5, 10 mg/kg, s.c.) markedly increased IL-10 in synoviocytes at protein and transcription level. Conclusion : The results indicate that CMA has a beneficial effect on rat AA due to modulating inflammatory cytokine production of synoviocytes, which play a crucial role in the pathogenesis of this disease.

• Journal of Microbiology and Biotechnology
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• v.11 no.2
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• pp.234-241
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• 2001

The C-terminal 393 bp region of the human interleukin-16 (IL-16) gene was cloned and expressed in E. coli along with mammalian cell lines. Recombinant IL-16 expressed from E. coli was 22 kDa on SDS-PAGE and showed 260% of chemoattractant activity at a concentration of $0.1\;{\mu}g/ml$. HeLa, COS, and Neuro-2a cells were transduced by recombinant retrovirus vector pLNC/IL-16/IRES/TK and the intracellular and secreted amounts of IL-16 produced by HeLa/IL-16/TK, COS/IL-16/TK, and Neuro-2a/IL-16/TK cells were determined by enzyme-linked immunosorbent assay (ELISA). HeLa/IL-16/TK $(1{\times}10^5)$ and COS/IL-16/TK $(1{\times}10^5)$ cells secreted 36.1 and 13.3 ng of IL-16 for 48 h, respectively. Forty-nine ng and 86.4 ng of IL-16 remained in the cell lysates of HeLa/IL-16/TK and COS/IL-16/TK. Intracellular and secreted amounts of IL-16 from Neuro-2a/IL-16/TK $(5{\times}10^5)$ cells during 24 h cultivation were 50 ng and 3.3 ng, respectively. Also, HeLa and COS cells wee stably transfected with mammalian expression vector pCRIII/IL-16. Both culture media and cell lysates prepared from HeLa/IL-16 cells and COS/IL-16 cells showed chemoattractant activity ranging from 190% to 460% as compared to the control experiment. Expression of the herpes simplex virus thymidine kinase (HSV0tk) gene in pLNC/IL-16/ IRES/TK bicistronic retroviral expression vector was verified by performing a genciclovir (GCV) sensitivity assay. Finally, IL-16 repressed Tat-transactivated human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) promoter activity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.942-952
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• 1998

The aim of this study was to evaluate spontaneous and LPS stimulated proinflammatory cytokines and chemokine release of alveolar macrophages in the patients with pulmonary tuberculosis and healthy individuals, as a control. Alveolar macrophages recovered from bronchoalveolar lavage fluids were cultured with or without LPS 0.1, 1, or 10 ${\mu}g/ml$ for 24 and 48 hours in 37C, 5% CO2. TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 amount were evaluated using ELISA kit from the supernatants. There were a significant increase in the spontaneous 24 hours release of TNF-$\alpha$ and IL-6 from the involved segments of tuberculosis patients compared with uninvolved segments and normal control There were also increasing trends of release of them after LPS stimulation in involved segments, but not significant. IL-1$\beta$ and IL-8 were not evaluated from the involved segments of tubeculosis and there were not significant differences of them between uninvolved segments of tuberculosis and normal control. It is concluded that cytokine release of alveolar macrophages in the pulmonary tuberculosis was markedly increased, and it was localized to the alveolar macrophages from the involved segments.

• Korean Journal of Plant Resources
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• v.22 no.5
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• pp.431-437
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• 2009

To investigate the anti-inflammatory effect of Ephedrae Herba in vivo and in vitro acute inflammation was induced by lipopolysaccharide (LPS) shock in rats fed Ephedrae Herba extracts and inflammatory cytokine concentrations were examined. In addition, the effect of Ephedrae Herba extracts on the production of inflammatory cytokines was examined in LPS-stimulated Raw 264.7 cells. In an in vivo experiment, plasma interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) concentrations were increased at 2 h and reached to maximal levels at 5 h after LPS treatment in all groups. Compared with control group, plasma IL-$1{\beta}$, IL-6, and TNF-$\alpha$ levels were lowered at 5 h after LPS treatment, but plasma IL-10 level was higher in at 2 and 5 h after LPS treatment in Ephedrae Herba extract group. In an in vitro experiment using Raw 264.7 macrophages, IL-$1{\beta}$, IL-6 and TNF-$\alpha$ concentrations in the Ephedrae Herba extract group were lower than those in control group. Compared with control group, IL-10 concentration appeared to be higher in the Ephedrae Herba extract group, but this trend was not significant. In conclusion, these results suggested that functional compound (s) in Ephedrae Herba extract may play a role in alleviating inflammatory response.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.568-575
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• 2000

Background : Cytokines are chemical mediators that control and modulate many inflammatory processes. They work in different fashions in a variety of diseases. Discriminating between malignant effusion, tuberculous effusion, and parapneumonic effusion are crucial from the clinical view-point in Korea. In the current study, interferon-gamma (IFN-${\gamma}$), soluble interleukin-2 receptor (IL-2R), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured for this purpose. Methods : Pleural fluids from patients with malignant disease, tuberculosis, parapneumonic effusion and lung empysema were collected and gauged using commercial ELISA kits. Results : 34 patients were enrolled in this study. Among these 15 cases were malignant effusions, 12 were tuberculosis pleurisy and 7 were parapneumonic effusion and lung empyema. The levels of cytokines measured in this study were as follows, in order of frequency, malignant effusion, tuberculous effusion, parapneumonic effusion and lung empyema. The levels of INF-${\gamma}$ were higher in tuberculous effusion than in malignant or parapneumonic effusion ($295.5{\pm}585.5$ vs. $16.7{\pm}50$ vs. $10.0{\pm}0$ pg/ml, p>0.05). The levels of IL-2R were higher in tuberculous effusion than in malignant or parapneumoruc effusion ($7423.5{\pm}3752.8$ vs. $3247.4{\pm}1713.3$ vs. $3790.2{\pm}3201.1$ pg/ml, p<0.05). No significant differences were found in the levels of IL-6 between the groups ($600{\pm}12.8$ pg/ml in malignant effusion, $556.4{\pm}161.7$ pg/ml in tuberculous effusion, $514.4{\pm}224.8$ pg/ml in parapneumoruc effusion). IL-10 levels were higher in parapneumoruc effusion than in malignant or tuberculous effusions ($98.4{\pm}141.7$ vs. $28.2{\pm}55.5$ vs. $11.3{\pm}11.7$ pg/ml, p<0.05). Conclusion : These results suggest that the measurement of IL-2R levels in pleural fluids may be a useful means of differentiating between tuberculous effusion and pleural effusions of other origins, and that the measurement of IL-10 levels in pleural fluids may be useful to differentiate between parapneumonic effusion and pleural effusions of other origins.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.135-140
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• 2010

Acorns have been used as a traditional remed as well as food source. However, few studies on their immunomodulating effects have been reported. In this study, the combined immunomodulative effect of a water extract of acorns was tested on seven to eight weeks old mice(balb/c). The mice were fed ad libitum on a chow diet, and a water extract of the plant mixture was orally administered every other day for four weeks at two different concentrations(50 and 500 mg/kg B.W.). The production of cytokine(IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$), secreted by macrophages stimulated with LPS or not, detected by ELISA assay using cytokine kit. After 48 h of incubation with mitogen(ConA or LPS) ex vivo study showed that cytokine (IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$) was detected in both of the 50 and 500 mg/kg B.W. supplementation groups with LPS stimulation. The results of this study may suggest that supplementation with acorn water extract increase immune function by regulating cytokine production capacity by activated macrophages.

• Korean Journal of Plant Resources
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• v.29 no.3
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• pp.305-312
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• 2016

This study examined the effects of trifoliate orange extract (TOE) on inflammatory reactions at the time of an LPS shock by performing experiments on rats injected with trifoliate orange extract and in Raw 264.7 cell cultures, with the aim of developing a new anti-inflammatory medicine. The IL-1β, IL-6, and TNF-α concentrations were lower in all of the groups treated with TOE than in the control group after 5 h of LPS treatment. The IL-10 concentration was higher in the 300-㎎/㎏ TOE group than in the control group after 2 h and 5 h of LPS treatment. The liver concentrations of cytokines IL-1β and IL-6 decreased more in the groups treated with TOE than in the control group and the IL-6 concentration did not differ significantly between the 100-㎎/㎏ TOE group than in the control group. The TNF-α and IL-10 concentrations did not differ significantly between the TOE groups and the control group. In the experiments involving Raw 264.7 macrophage cultures subjected to LPS shock, the productions of IL-1β, IL-6, and TNF-α decreased in all of the groups treated with TOE compared to the control group. The IL-10 concentration did not differ significantly between the groups treated with TOE and the control group. Together the findings of this study suggest that TOE contains functional substances that can influence inflammatory reactions.

• The Korean Journal of Food And Nutrition
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• v.21 no.2
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• pp.204-209
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• 2008

The present study examined the ex vivo effect of Job's tear on immune function. Seven to eight week old mice(Balb/c) were fed a chow diet ad libitum two different concentrations (50 and 500 mg/kg BW) of water extract of Job's tear were orally administ every other day for two weeks. The results indicated that macrophage activation had occurred in the mice receiving 50 mg/kg B. W. of Job's tear water extract. Overall, using a mouse model, this study demonstrated that Job's tear extract may enhance immune function by regulating the $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ and IL-10 cytokine production capacity of activated macrophages in mice. This study may suggest that supplementation of Job's tear water extracts may enhance the immune function by regulating the enhancing the cytokine production by activated macrophage ex vivo.