• Journal of Life Science
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• v.17 no.7 s.87
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• pp.923-930
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• 2007

Thymus can regenerate to its normal mass within 14 days after acute involution induced by cyclophosphamide (CY) in adult rat. Despite the established role of Wnt pathways in the process of thymus development, they have not yet been associated with the regeneration of adult thymus. The purpose of this study was to investigate whether Wnt7b, which is expressed in developing thymic epithelial cells rather than in thymocytes, is modulated during thymic regeneration in adult rat. Here, we show that Wnt7b expression was up-regulated in the regenerating thymus. Cells immunolabeled for the Wnt7b were identified as macrophages. Furthermore, Wnt7b gene expression was decreased by the treatment of receptor activator of NF-kappaB ligand (RANKL). Taken together, our results demonstrate that Wnt7b gene expression was increased in macrophages during thymic regeneration and negatively regulated by RANKL.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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• pp.28-34
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• 1999

Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.443-449
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• 2001

Previously we reported that THI 52 inhibits tumor necrosis factor $(TNF)-{\alpha}$ mRNA expression in mouse peritoneal macrophages exposed to LPS plus $IFN-{\gamma}.$ In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus $IFN-{\gamma}.$ Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.40-45
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• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.192-192
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• 1996

Endothelin has $ET_{A}$ type and $ET_{B}$ type receptors, and it has been thought that ET-1 proves vasoconstriction effect via $ET_{A}$ receptor and vasodilation via $ET_{B}$ receptor. Recently, it has been reported that $ET_{B}$ receptor is also related to the vaso-constriction. Bosentan is a $ET_{A+B}$ receptor antagonist, and proves it's effect on trauma and ischemia. We already announced that the level of Endothelin-1 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of Bosentan, $ET_{A+B}$ receptor antagonist, (300nmol/body) was done for observing the role of endothelin-1 on the pathogenesis of EAE. Bosentan ameliorated the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model suggests that Bosentan is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• Natural Product Sciences
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• v.25 no.4
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• pp.304-310
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• 2019

The stems of Oplopanax elatus (OE) have long been used to treat inflammatory disorders in herbal medicine, and in the previous investigation, OE was found to possess anti-inflammatory activity in lipopolysaccharide-treated macrophages, RAW 264.7 cell. OE reduces inducible nitric oxide (NO) synthase-induced NO production, and interferes with mitogen-activated protein kinase activation pathways. In the present study, the pharmacological action of the water extract of OE was examined to establish anti-arthritic action, using a rat model of adjuvant-induced arthritis (AIA). The water extract of OE administered orally inhibited AIA-induced arthritis at (100 - 300) mg/kg/day. The paw edema was significantly decreased, in combination with reduced production of pro-inflammatory cytokines. The action mechanism includes an inhibition of MAPKs/nuclear transcription factor-κB activation. These new findings strongly suggest that OE possesses anti-arthritic action, and may be used as a therapeutic agent in inflammation-related disorders, particularly in arthritic condition.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1386-1390
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• 2005

Lycii Fructus (LF) has been reported to possess various biological activities. In this study, we investigated the anti-inflammatory and anti-allergic effects of LF extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells and rat peritoneal mast cells(RPMC). LF extract inhibited NO production and the expressions of inducible NO synthase (iNOS) mRNA and enzyme protein, determined by Griess reactions, RT-PCR and Western blotting, respectively, in LPS-stimulated RAW 264.7 macrophages cells. LF extract significantly inhibited histamine release in compound48/80 stimulated rat peritoneal mast cells compared with the compound48/80 only treated cells. It is suggested that the LF extract can improve the inflammation status that involves the histamine release.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.538-544
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• 1999

To elucidate the involvement of interleukin-$1{\beta}$ converting enzyme (ICE) in the course of experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunizing rats with an emulsion of rat spinal cord homogenate with complete Freund's adjuvant supplemented with Mycobacterium tuberculosis (H37Ra, 5mg/ml) and then examined the expression of ICE in the spinal cord of rats with EAE. In normal rat spinal cords, ICE is constitutively, but weakly, expressed in ependymal cells, neurons, and some neuroglial cells. In EAE, many inflammatory cells are positive for ICE, and the majority of ICE+ cells were identified as ED1+ macrophages. During this stage of EAE, the number of ICE+ cells in brain cells, including neurons and astrocytes, increased and these cells also had increased ICE immunoreactivity. These findings suggest that the upregulation of ICE in both brain cells and invading hematogenous cells is stimulated by a secretory product from inflammatory cells, and that this enzyme is involved in the pathogenesis of EAE via the production of IL-1 beta.

• Korean Journal of Animal Reproduction
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• v.25 no.1
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• pp.43-49
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• 2001

This study was performed to elucidate the effects of copper poisoning on the reproductive organ of rats. After consecutive oral administrations of copper sulfate, the weights of testis, the numbers and motilities of sperms, organ weights and histological changes of testes were compared between control and experimental groups. 1. Testis weights of 1,000, 2,000 or 4,000 ppm/kg of copper sulfate-administrated rats gradually decreased compared with control group, and the values no significant changes. 2. The sperm numbers of 1,000, 2,000 or 4,000 ppm/kg of copper sulfate-administrated rats were lowered in dose dependent manners than those of control group's and the values no significant changes. 3, The motilities sperms of 1,000, 2,000 or 4:000 ppm/kg of copper sulfate-administrated rats decreased significantly in dose-dependent manners compared with those of control group's. 4. The weights of livers and kidneys of 1,000, 2,000 or 4,000 ppm/kg of copper sulfate-administration rats decreased or increased. 5. Necrosis of hepatocytes around the central veins and infiltrations of fine granules-harboring macrophages in periportal and interstitial tissues were found out in the livers of copper sulfate-administrated rats. The Bowman's capsule and tubules of kidneys were filled with hyaline material.