• Journal of Veterinary Clinics
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• v.31 no.6
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• pp.469-476
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• 2014

The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-naïve and LPS-stimulated RAW 264.7 macrophages and to examine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-${\alpha}$) production, and nuclear factor-kappa B (NF-${\kappa}B$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-${\alpha}$ in LPS-naïve RAW 264.7 cells. The CLA-induced TNF-${\alpha}$ production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-${\kappa}B$ and $PPAR{\gamma}$ in LPS-naïve RAW 264.7 cells, and this effect was abolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROS production. LPS increased both TNF-${\alpha}$ production and NF-${\kappa}B$ activity, whereas t10c12-CLA reduced TNF-${\alpha}$ production and NF-${\kappa}B$ activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production and NF-${\kappa}B$ activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ activation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected $PPAR{\gamma}$ activity in LPS-stimulated RAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-${\alpha}$ production by increasing ROS production in LPS-naïve RAW 264.7 cells, which is mediated by the enhancement of NF-${\kappa}B$ activity via $PPAR{\gamma}$ activation. By contrast, t10c12-CLA suppresses TNF-${\alpha}$ production by inhibiting ROS production and NF-${\kappa}B$ activation via a $PPAR{\gamma}$-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-${\alpha}$ production and NF-${\kappa}B$ activation through formation of ROS in RAW 264.7 macrophages.

• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.261-270
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• 2018

The aim of this study was to evaluate the antitumor activities of Typhae pollen (TP) by confirming in vitro cytotoxicity and in vivo anti-tumor and immune-modulatory effect with anti-cachexia effect. The MTT assay is used in HepG2 cell to detect potential cytotoxic activities of aqueous extract of Typhae pollen (TPe). After HepG2 tumor cell implantation, eight mice per groups were assigned to six groups. Three different dosages of TPe (500, 250 and 125 mg/kg) were orally administered in the amount of $10m{\ell}/kg$ and sorafenib also administered 20mg/kg, every day for 35 days from 28 days after the tumor cell implantation. We observed the changes on body weights, tumor volume and weights, lymphatic organ, serum interferon $(IFN)-{\gamma}$ levels, splenocytes and peritoneal NK cell activity, splenic tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-10 contents. Periovarian fat weights, serum IL-6 levels, thicknesses of deposited periovarian adipose tissue and mean diameters were also detected to monitor the tumor-related anticachexic effects. In tumor masses, the immunoreactivities of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (cleaved PARP) - apoptotic marks, cyclooxygenase-2 (COX-2), inducible nitric oxide synthases (iNOS) and tumor necrosis factor $(TNF)-{\alpha}$ were additionally observed by immunohistochemistry. The results were compared with sorafenib. Decreases of COX-2 were demonstrated in sorafenib and TPe treated mice and also increases of iNOS in tumor masses were observed in TPe, not in sorafenib. TPe increased periovarian fat pad weights compared with tumor-bearing controls and sorafenib treated mice. TPe showed increases of splenic $TNF-{\alpha}$, IL-10 and $IL-1{\beta}$, serum $IFN-{\gamma}$ and NK cell activities corresponding to increases of spleen weights, lymph node weights and non-atrophic changes of lymph nodes. Our results show oral treatment of TPe 500, 250 and 125 mg/kg has potent in vitro and in vivo antitumor activities through modest cytotoxic effects, immunomodulatory effects and apoptotic activities in HepG2 tumor cells. In addition, TPe can prevent cancer related cachexia.

• Molecules and Cells
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• v.25 no.4
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• pp.531-537
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• 2008

Abnormal activation of nuclear factor kappa B ($NF-{\kappa}B$) probably plays an important role in the pathogenesis of Duchenne's muscular dystrophy (DMD). In this report, we evaluated the efficacy of curcumin, a potent $NF-{\kappa}B$ inhibitor, in mdx mice, a mouse model of DMD. We found that it improved sarcolemmic integrity and enhanced muscle strength after intraperitoneal (i.p.) injection. Histological analysis revealed that the structural defects of myofibrils were reduced, and biochemical analysis showed that creatine kinase (CK) activity was decreased. We also found that levels of tumor necrosis factor alpha ($TNF-\alpha$), interleukin-1 beta ($IL-1\beta$) and inducible nitric oxide synthase (iNOS) in the mdx mice were decreased by curcumin administration. EMSA analysis showed that $NF-{\kappa}B$ activity was also inhibited. We thus conclude that curcumin is effective in the therapy of muscular dystrophy in mdx mice, and that the mechanism may involve inhibition of $NF-{\kappa}B$ activity. Since curcumin is a non-toxic compound derived from plants, we propose that it may be useful for DMD therapy.

• Journal of Marine Bioscience and Biotechnology
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• v.2 no.2
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• pp.86-93
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• 2007

Chronic inflammation has been known to have a close relationship with several diseases including periodontitis, colitis, hepatitis and arthritis. Recently anti-inflammatory agents have been developed from marine natural resources. In this study, Ecklonia cava (EC) was found to have anti-inflammatory effect. Ethanolic extract of EC belonging to brown algae exhibited an excellent inhibitory effect on the production of inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6 and prostaglandin $E_2$ by RA W264.7 cells. Furthermore, in reporter gene assay and western blot analysis, EC extract exerted anti-inflammatory effect via inactivation of NF-${\kappa}B$ transcription factor that regulates the expression of these inflammatory mediators in macrophages. In addition, EC extract inhibited the activity of matrix metalloproteinase that play an important role in chronic inflammation. These results suggest that EC extract may provide a pharmaceutical potential in inhibiting chronic inflammation.

• Clinical and Experimental Pediatrics
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• v.53 no.1
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• pp.41-47
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• 2010

Purpose : Adiponectin is an endogenous modulator of vascular remodeling that suppresses vascular inflammation. However, the role of adiponectin in Kawasaki disease (KD) has not been elucidated. The purpose of this study is to investigate the correlation between serum adiponectin level and several parameters, such as interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, lipid profile, and C reactive protein (CRP), and to clarify the association between adiponectin and cardiac function. Methods : Twenty-two KD patients (22 patients in acute phase and 20 patients in subacute phase) were enrolled in the study group. The control group consisted of 31 subjects (13 febrile patients and 18 healthy children). Both groups underwent blood sampling and tissue Doppler imaging (TDI). Results : CRP was significantly increased in the KD group compared with the control group. There were no significant differences in serum $TNF-{\alpha}$, IL-6, and adiponectin levels between groups. However, a negative correlation was found between adiponectin level and CRP level or platelet count. Systolic myocardial velocity and A myocardial velocity measured by TDI were decreased significantly in the acute KD group compared with the subacute KD group and control group. Positive correlations were found between adiponectin level and systolic myocardial velocity or A myocardial velocity. Conclusion : In acute KD patients, low adiponectin level was related to severe inflammatory reactions and decreased left ventricular functions.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.161-171
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• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.987-990
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• 2006

Intravenous immunoglobulin (IVIG) infusion is an effective therapy for acute Kawasaki disease (KD). Nonetheless, approximately 10 percent to 20 percent of patients have persistent or recrudescent fever despite IVIG treatment, leading to a higher risk for coronary artery aneurysms (CAA). This unresponsiveness may pose a challenge to the clinicians. Tumor necrosis $factor-{\alpha}$ levels are elevated in the acute phase of the disease, especially in patients who develop CAA. We report a 10-month-old male with KD who failed to respond to multiple doses of IVIG and methylprednisolone and who then was treated with infliximab (5 mg/kg single dose). After infliximab treatment, he became afebrile with normalization of inflammatory markers and no further progression of CAA.

• Preventive Nutrition and Food Science
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• v.8 no.3
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• pp.239-244
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• 2003

Recently, we reported (J Korean Soc Food Sci Nutr, 31(3): 516-520, 2002) that Semisulcospira libertina (Marsh Snail) pretreatment has a hepatoprotective effect on $CCl_4$-induced liver damage in rats. The purpose of this study was to investigate the possible mechanisms of hepatoprotection by S. libertina (SL) on liver injury induced by acetaminophen (AA). Male ICR mice were pretreated with dehydrated powder of SL once daily for three consecutive days, given a single toxic dose of AA (450 mg/kg) and liver function determined 24 h later. Liver damage was assessed by quantifying serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) activities, and by measuring hepatic lipid peroxidation. To confirm possible mechanism(s), the content of hepatic glutathione (GSH) and gene expression of tumor necrosis factor a (TNF $\alpha$) mRNA by reverse transcription-polymerase chain reaction (RTPCR) were also measured. Pretreatment with SL dramatically lowered AA-elevated ALT, AST and SDH activities. SL pretreatment decreased AA-produced lipid peroxidation by 11% and restored the AA-depleted hepatic GSH by 27%. Furthermore, SL markedly suppressed the expression of TNF $\alpha$ mRNA induced by AA. Our findings revealed that the possible hepatoprotective mechanisms of SL could be attributed, at least in part, to the glutathione-mediated detoxification as well as the regulation of TNF $\alpha$ mRNA expression.

• Journal of Microbiology and Biotechnology
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• v.16 no.4
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• pp.576-583
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• 2006

The alkali-soluble glucan of the yeast cell wall contains $\beta-(1,3)-$ and (1,6)-D-linkages and is known to systemically enhance the immune system. In the previous study [6], in order to isolate cell wall mutants, a wild-type strain was mutagenized by exposure to ultraviolet light, and the mutants were then selected via treatment with laminarinase $(endo-\beta-(1,3)-D-glucanase)$. The mass of alkali- and water-soluble glucans produced by the mutant was measured to be 33.8 mg/g of the dry mass of the yeast cell. Our results showed that the mutants generated the amount of alkali-soluble glucan 10-fold higher than that generated by the wild-type. Structural analysis showed that the alkali-soluble glucan from the mutants was associated with a higher degree of $\beta-(1,6)-D-linkage$ than was observed in conjunction with the wild-type. Yeast cell wall $\beta-glucan$ was shown to interact with macrophages via receptors, thereby inducing the release of tumor necrosis factor alpha $(TNF-\alpha)$ and nitric oxide. Alkali-soluble $\beta-glucans$, both from water-soluble and water-insoluble glucan, exhibited a higher degree of macrophage activity with regard to both the secretion of tumor necrosis factor alpha $(TNF-\alpha)$ and nitric oxide and direct phagocytosis, than did the positive control ($1{\mu}g$ of lipopolysaccharide).