This study was to investigate the effects of high-fat diet feeding for a very long period of time on gene expression of inflammatory cytokines in mouse adipose tissue and to determine whether caloric restriction (CR) or insulin sensitizer treatment changes the cytokine gene expressions even in obese mice fed a high-fat diet for a very long term-period. Gene expression levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were examined by real-time PCR in subcutaneous abdominal adipose tissue (SubQ) from obese and non-obese male C57BL/6 mice at 16, 26, 36, 47, and 77 weeks of age on either normal diet (ND) or high-fat diet (HFD) after starting at 6 weeks of age. In addition, gene expression levels of TNF-${\alpha}$, IL-6 and MCP-1 were determined in SubQ before and after rosiglitazone treatment or CR on 47-week-old obese mice. The results demonstrated that gene expression levels of TNF-${\alpha}$, IL-6 and MCP-1 were significantly increased with aging in SubQ of mice in both groups of diet. MCP-1 gene expression of SubQ in all ages tested was significantly or marginally increased in mice on HFD compared with ND. While TNF-${\alpha}$ expression was significantly reduced by rosiglitazone, IL-6 and MCP-1 were significantly decreased by CR. The basic data in this study will be useful for characterizing the C57BL/6 mouse as an animal model of obesity induced by high-fat diet feeding for a very long period of time, and a better understanding of inflammatory cytokine regulation in diet induced obesity which may facilitate the development of new therapeutic strategies to prevent the complications of obesity.
Chunghyul-dan (CHD) is a combinatorial drug known to exert anti-inflammatory effects in endothelial cells. In this study, we employed global transcriptional profiling using cDNA microarrays to identify molecular mechanisms responsible for the anti-inflammatory activity of CHD in endothelial cells. An analysis of the microarray data revealed that transcript levels of monocyte chemotactic protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1) and activated leukocyte cell-adhesion molecule were dramatically altered in CHD-treated endothelial cells. These changes in gene expression were confirmed by RT-PCR, Western blotting and ELISA. Chronic CHD treatment also appeared to decrease MCP-1 secretion, probably as a result of decreased MCP-1 expression. In addition, we determined that chronic CHD treatment inhibited lipopolysaccharide-stimulated adhesion of THP-1 leukocytes to endothelial cells. The inhibitory effect of CHD on LPS-stimulated adhesion resulted from downregulation of VCAM-1 expression. Transmigration of THP-1 leukocytes through endothelial cells was also inhibited by chronic CHD treatment. In conclusion, CHD controls a variety of inflammatory activities by regulating MCP-1 and VCAM-1 gene expression.
Background: Tuberculosis has commonly been associated with various hematologic changes. A difference between the changes found in pulmonary tuberculosis and those found in miliary tuberculosis has been discussed. Up to now some worker were investigated hematological changes associated with pulmonary tuberculosis but was not investigated those associated with miliary tuberculosis in korea. Therefore we examimed the peripheral blood and bone marrow findings in miliary tuberculosis patients to determine hematologic changes. Methods: We performed blood sample at admission and bone marrow biopsy within 7days after admission. For evaluation of the hematologic findings, full blood counts and marrow differential counts were defined by the criteria outlined by Dacie and Lewis. Results: 1) Peripheral blood findings: Pancytopenia in 10% of patients, anemia in all patients, leukocytosis in 10% of patients, leukopenia in 20% of patients, thrombocytopenia in 30% of patients, lymphocytopenia in 90% of patients, monocytosis in 40% of patients and neutrophilia in 10% of patients were found at peripheral blood. 2) Bone marrow findings: Lymphocytopenia in 30% of patients, lymphocytosis in 20% of patients, plasmacytosis in 40% of patients, monocytosis in 100% of patients, and hypocellularity in 30% of patients were found at bone marrow. Erythropoiesis was decreased in 30% of patients. Granulopoiesis was decreased in 20% of patients and increased in 20% of patients. Bone morrow granuloma occured in 25% of patients. Conclusion: Hematologic changes of miliary tuberculosis were seen tendency of cytopenic pattern but monocyte was increased at peripheral blood and bone morrow. This findings would provide additional information for the differential diagnosis of miliary tuberculosis.
The objective of present study was to investigate the effect of Baikal Skullcap (Scutellaria baicalensis Georgi) extracts on recovery of liver function in $CCl_4$-exposed rats. The values of RBC, Hb and PCV did not show significant difference among all treatment groups. The counts of WBC was lower in Skullcap extracts groups than in control group. The ratio of neutrophils and eosinophiles were decreased, and the ratio of lymphocytes and monocytes were increased with increased administration of Skullcap extracts dosage. The ratio of basophils was, however, not significantly different among all treatment groups. The concentration of plasma total protein and albumin showed no significant difference among all treatment groups. The ratio of albumin/globulin was higher in Skullcap extracts groups than in control group. The activities of GOT, GPT and LDH were lower in Skullcap extracts groups, compared to control group. The liver IL-$1{\beta}$, IL-6 and TNF-$\alpha$ concentration were decreased, and IL-10 was increased in Skullcap extract groups, compared to control group. Results of this study suggested that Skullcap may alleviate liver inflammatory reaction induced by liver toxicity.
Kim, Heui-Soo;Jeon, Seung-Heui;Yi, Joo-Mi;Kim, Tae-Hyung;Lee, Won-Ho
Journal of Life Science
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v.13
no.3
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pp.291-297
/
2003
A human endogenous retroviral family (HERV-W) has recently been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Two pol fragments (HWP-FB10 and HWP-FBl2) of HERV-W family were identified and analysed by the PCR approach with cDNA library of human fetal brain. They showed 89 percent nucleotide sequence similarity with that of the HERV-W (accession no. AF009668). Deletion/insertion or point mutation in the coding region of the pol fragments from human fetal brain resulted in amino acid frameshift that induced a mutated protein. Phylogenetic analysis of the HERV-W family from GenBank database indicates that the HWP-FB10 is very closely related to the AC000064 derived from human chromosome 7q21-q22. Further studies on the genetic relationship with neighbouring genes and functional role of these new HERV-W pol sequences are indicated.
The present study was sought to clarify whether the combination of mental activity with subway noise affects hematological variables. Fifty-six healthy volunteers participated in this experiment and underwent a stress task consisting of combination_of mental activity (mental arithmetic) with subway noise for 50 min and 60min of recovery after the end of the stress task. Venous blood samples were collected for measuring CBC, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), fibrinogen concentration, D-dimer and high sensitive C-reactive protein (H-CRP) levels before (baseline), 50min of stress task (S-50m), and 60 min of recovery (R-60m). Total leukocyte, neutrophil and lymphocyte counts significantly increased at R-60m compared with baselines. RBC count at S-50m was higher, while monocyte counts at S-50m and R-60m were lower than those of baselines. aPTTs shortened at S-50m and R-60m, but PT reduced at R-60m as compared with baselines. D-dimer and H-CRP levels at S-50m and R-60m were significantly higher than those of baselines. These findings imply that a combination of mental activity with subway noise nay cause leukocytosis, homo-concentration, shortened PT and aPTT, decreased ESR, and raised D-dimer and H-CRP levels, suggesting possible development of inflammation and prothrombogenic reaction attributable to a subway environment.
Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.
Journal of Physiology & Pathology in Korean Medicine
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v.20
no.5
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pp.1337-1345
/
2006
Hypercholesterolemia is a pivotal pathogenic factor for the development and maintenance of atherosclerosis. The present study was designed to evaluate whether the methanol extract of Sorbus commixta cortex (MSC) restores vascular dysfunction in association with the aortic expressions of proinflarnmatory and adhesion molecules in high cholesterol (HC) diet-rats. Chronic treatment with low (100 mg/kg/day) or high doses (200 mg/kg/day) of MSC lowered the increase in plasma levels of triglyceride (TG) and low-density lipoprotein (LDL) cholesterol induced by a cholesterol-enriched diet without affecting on the plasma level of high density lipoprotein (HDL)-cholesterol. Vascular tone attenuated in the HC-diet rats was restored by administration with MSC. Treatment with MSC also suppressed the HC-induced increase in the monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-$_K$B (NF-$_K$B) p65 expressions as well as expressions levels of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (ICAM-1), and E-selectin in aorta. The present study also showed that MSC inhibited the HC-mediated induction of ET-1 and ACE expression. In histopathological examination, aortic segments in the HC-diet rat revealed thickening intima and media, which were blocked by administration with MSC. Taken together, MSC could suppress the development of atherosclerosis in the HC-diet rat model through the inhibition of the aortic expression levels of pro-inflammatory and adhesion molecules.
Journal of Physiology & Pathology in Korean Medicine
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v.20
no.5
/
pp.1159-1165
/
2006
This study was done to investigate the effects of Gamisojaganggi-tang(GSGT) on immunopathologic changes in OVA-induced asthma model of mice. Pathologic indicators associated with this immune disease, which include cytokines, the number of immune-cells, immunoglobin E (IgE), were examined, and histological changes of bronchial tissues were also examined. The administration of GSGT significantly reduced the lung weight compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of total cells in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of eosinophil in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly increased the number of monocyte in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of lymphocyte in BAL compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the gene expression of eotaxin in lung tissue compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly reduced the IL-4 and IL-5 production in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly reduced the levels of total IgE and ovalbumin-specific IgE in BALF. The administration of GSGT significantly reduced the levels of ovalbumin-specific IgE whereas the serum levels of total IgE were insignificantly reduced compared with control mice of OVA-induced asthma model. The administration of GSGT moderately reduced bronchial alveolar narrowing, bronchiovascular edema and increase in the size of alveolar space, which shown in control mice of OVA-induced asthma model, in a dose dependent manner. Furthermore, GSGT reduced invasion of inflammatory cells, and proliferation of smooth muscle cells in bronchial tissue. These results suggested that GSGT has suppressive effects on pathologic changes associated with disease progression in asthma through the modulation of immune system. GSGT has potential to use as an anti-asthmatic agents.
Kim, Seung-Tae;Kim, Yun-Ju;Lee, Hyang-Sook;Choi, Sun-Mi;Yin, Chang-Shik;Lee, Ji-Young;Park, Hi-Joon;Lee, Hye-Jung
Korean Journal of Acupuncture
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v.26
no.2
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pp.27-38
/
2009
Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, principally characterized by synovial inflammation of the joints. We previously reported the effect of acupuncture for RA, but the mechanism is still unclear. Various factors such as oxidative stress and angiogenesis were involved in the pathogenesis of RA, and recently, it has also been reported that cytokines also play a major role in RA. Thus, we investigated whether acupuncture could induce any changes in the levels of cytokines including vascular endothelial growth factor (VEGF), angiogenin and epidermal growth factor (EGF) as well as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF) in the sera of RA patients. Methods: The forty three patients who met the American College of Rheumatology (ACR) criteria for RA recruited. The acupuncture group (n=21) underwent 14 sessions of partially individualized acupuncture treatment for 6 weeks, and the control group had no treatment (n=13) over the same periods. We evaluated ESR, CRP and RF. In addition, to find out the mechanism of acupuncture, we assessed the changes of the cytokine activities using protein cytokine array in the sera of the patients. Results: Acupuncture significantly decreased the levels of ESR and CRP, but RF were not changed after 6-week acupuncture treatments. Moreover, acupuncture reduced the levels of VEGF, angiogenin and EGF in the sera of the patients. Interestingly, they were related with angiogenesis, which is an important process in the pathogenesis of RA. The levels of oncostatin, interleukin(IL)-$1{\alpha}$, IL-8, leptin, monocyte chemotactic protein-1, macrophage-derived chemokine, macrophage inflammatory proteins-1, platelet-derived growth factor BB and RANTES were not changed significantly. Conclusions: The effect of acupuncture for reliving RA symptoms can be partially explained by inhibition of angiogenesis factors in the sera of the RA patients.
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