• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6441-6446
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• 2012

Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury.

• IMMUNE NETWORK
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• v.15 no.1
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• pp.37-43
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• 2015

It is well established that TGF-${\beta}1$ and retinoic acid (RA) cause IgA isotype switching in mice. We recently found that lactoferrin (LF) also has an activity of IgA isotype switching in spleen B cells. The present study explored the effect of LF on the Ig production by mouse peritoneal B cells. LF, like TGF-${\beta}1$, substantially increased IgA production in peritoneal B1 cells but little in peritoneal B2 cells. In contrast, LF increased IgG2b production in peritoneal B2 cells much more strongly than in peritoneal B1 cells. LF in combination with RA further enhanced the IgA production and, interestingly, this enhancement was restricted to IgA isotype and B1 cells. Similarly, the combination of the two molecules also led to expression of gut homing molecules ${\alpha}4{\beta}7$ and CCR9 on peritoneal B1 cells, but not on peritoneal B2 cells. Thus, these results indicate that LF and RA can contribute to gut IgA response through stimulating IgA isotype switching and expression of gut-homing molecules in peritoneal B1 cells.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.177-184
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• 2020

Objectives : Postpartum depression is known to occur in 10-15% of mothers. The concentration of cytokine varies depending on stress, depression, pregnancy and general medical conditions. We hypothesized that the concentration of cytokines may be related to reproduction and childbirth, and that women with postpartum depression would show alterations in cytokines levels. Methods : A total of 104 pregnant women were selected as subjects, and 60 non-pregnant women were selected as normal controls. Symptoms of depression were evaluated in the pregnant study subjects using the diagnostic criteria outlined in the Edinburgh Postnatal Depression Scale (EPDS). The pregnant subjects were divided into three groups perinatal non-depression controls (n=61), postpartum depression-recovery (n=18), and postpartum depression (n=25). Results : The plasma concentration of TGF-β1, IGF-1 was higher in the pregnant group than in non-pregnant controls (TGF-β1 ; p<0.01, IGF-1 ; p=0.026). At 24 weeks of pregnancy and 6 weeks of delivery, there were no significant differences in the plasma concentration of TGF-β1, IGF-1, β-NGF, IL-2, IL-4, IL-6, IFN-γ, TNF-α between the three groups. There was no statistically significant difference in all three groups during the course of depression in pregnant women. Conclusions : This study found significant difference in plasma cytokines concentrations between non-pregnant controls and perinatal non-depression controls.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.127-130
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• 2002

The present study was aimed to investigate whether the adriamycin-induced nephrosis is associated with an altered regulation of local renin-angiotensin system (RAS) in the kidney. Rats were subjected to a single injection of adriamycin (2 mg/kg body weight, IV) and kept for 6 weeks to allow the development of nephrosis. They were then divided into two groups, and supplied with and without cilazapril, an angiotensin converting enzyme (ACE) inhibitor, in drinking water (100 mg/l) for additional 6 weeks. Another group without adriamycin-treatment served as control. The mRNA expression of renin, ACE, type 1 and type 2 angiotensin II receptors (AT1R, AT2R), and transforming growth factor $(TGF)-{\beta}1$ was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. Adriamycin treatment resulted in heavy proteinuria. Accordingly, the mRNA expression of renin, ACE, and AT1R was increased in the renal cortex, while that of AT2R was decreased. Co-treatment with cilazapril attenuated the degree of proteinuria. While not affecting the altered expression of renin, cilazapril decreased the expression of ACE to the control level. Cilazapril further increased the expression of AT1R, while it restored the decreased expression of AT2R. The expression of $(TGF)-{\beta}1$ was increased by the treatment with adriamycin, which was abolished by cilazapril. An altered expression of local RAS components may be causally related with the development of adriamycin-induced nephrosis, in which AT1R is for and AT2R is against the development of nephrosis.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.51-54
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• 2009

${\beta}ig$-h3, is a TGF-${\beta}$-induced gene product, extracellular matrix protein with 68 kDa MW(683 amino acids) and has been known for its possible roles in cell adhesion, spreading, migration and proliferation. To minimize a proteolytic degradation of ${\beta}ig$-h3, ${\beta}ig$-h3 incorporated chitosan sponge was prepared and its effects on fibroblast adhesion and migration were investigated. And its wound healing efficacy was evaluated in deep 2nd degree burn rabbit ear wound model. ${\beta}ig$-h3 enhanced fibroblast adhesion and proliferation. In histological observation, a significant over-proliferation of epidermal regeneration was observed in ${\beta}ig$-h3/chitosan dressing applied wound while epidermal regeneration was not proceeded yet in chitosan only treated wound. ${\beta}ig$-h3/sponge dressing could enhance epidermal regeneration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1127-1134
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• 2007

The study was designed to investigate the mechanism of Patholoobi Caulis freeze dried powder (PCF) on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats and cytokines production ($IL-1{\beta}$, $TNF-{\alpha}$, IL-10, $TGF-{\beta}$) in cerebral ischemic rats. The results in normal rats were as follows ; Increase of PCF-induced rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g/kg$, I.p.), an inhibitor of guanylate cyclase, and was inhibited by indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. Increase of PCF-induced MABP was decreased by pretreatment with methylene blue, but was increased by indomethacin. These results suggested that the mechanism of action PCF was mediated by cyclic 3',5'-guanosine monophosphate. The results in cerebral ischemic rats were as follows ; In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, PCF (10 mg/kg. i.p.) significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and increased IL-10 production compared with control group. In cytokine production in serum from femoral arterial blood 1 hr 1 hr after reperfusion, PCF (10 mg/kg, i.p.) significantly decreased $IL-1{\beta}$ production, and incresed IL-10 production compared with control group. These results suggested that PCF was significantly and stably increased regional cerebral blood flow by inhibiting $IL-1{\beta}$ production, and by accelerating IL-10 production.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.377-384
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• 2010

The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-${\beta}$, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-${\beta}$, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.

• Toxicological Research
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• v.26 no.4
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• pp.245-252
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• 2010

Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF)-$\beta$, Wnt, and Notch signaling pathways, have been shown to induce EMT. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Mounting evidence shows that EMT is associated with cell invasion and tumor progression. In this review, we summarize the characteristic features of EMT, pathways leading to EMT, and the role of EMT in cell invasion. Three topics are addressed in this review: (1) Definition of EMT, (2) Signaling pathways leading to EMT, (3) Role of EMT in cell invasion. Understanding the role of EMT in cell invasion will provide valuable information for establishing strategies to develop anti-metastatic therapeutics which modulate malignant cellular processes mediated by EMT.

• Journal of the korean veterinary medical association
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• v.32 no.1
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• pp.43-51
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• 1996

경구적으로 투여된 항원에 대해서 특이적으로 T세포의 기능과 항체산생이 억제되는 현상이 경구면역관용(oral tolerance)인 것이다. 지금까지 해석이 곤란하였던 이 현상에 대해서 최근 분자생물학적인 기법이 적용되기 시작한 결과, 이 현상에 관여하는 세포가 주로 $CD8^+$ T세포에의한 억제 혹은 $CD4^+$T세포의 불응답(unresponsiveness)에 기인하다는 것이 명백해졌다. 또한 각종 cytokine중 IFN$\gamma$, TGF$\beta$, IL-10 등이 이 현상에 있어 중요한 역할을 담당한다는 것이 밝혀지고 있다. 사실 경구면역관용은 말초면역관용을 야기한다는 것이 오래전부터 알려진 한 방도이다. 경구적으로 투여된 항원이 관용을 야기하는 일차적인 기전은 능동적인 억제의 발생 혹은 clone성 anergy(과민증에 대한 무감증)에 의거하는 것이다. 낮은 량의 경구투여항원은 능동적인 억제를 야기하기 쉬우나 반대로 높은 양의 경구투여항원은 clone성 anergy를 야기하는 경향이 있다. 능동적인 억제를 매개하는 조절세포는 경구면역관용에 의해서 격발된 후 TGF$\beta$및 IL-4와 같은 억제성 cytokine의 분비에 의해서 능동적 억제작용을 한다. 더구나 GALT(gut-associated lymphoid tissue)를 선별적으로 자극하는 항원은 Th2형 세포반응을 발생한다. 또한 이와같은 유도기구의 해석과 동시에 사람에서 면역반응의 이상으로 야기되는 관절 rheumatism이나 다발성경화증(multiple sclerosis) 그리고 각종 allergy도 이 경구면역관용을 이용하여 치료하는 것이 가능하게 되었다는 것이다.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.245-257
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• 2004

This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.