• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.112-119
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• 2024

Objective: Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. Methods: In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Results: Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). Conclusion: The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.438-442
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• 1997

Antisense oligonucleotide represents an interesting tool for selective inhibition of gene expression. However, their low efficiency of introduction within intact cells remains to be overcome. Antisense-$TGF{\beta}$ (25 mer) and antisense-$TGF{\beta}$ (18 mer) were used to study the cellular transport and biological function of antisense oligonucleotide in vitro. Since TGF and TNF play on important role in regulating the nitric oxide production from macrophages, the action of the above antisense oligonucleotides was easily monitored by the determination of nitrite. Poly-L-lysine, benzalkonium chloride and tetraphenylphosphonium chloride were used as polycations, which neutralize the negative charge of antisense oligonucleotide. The production of nitric oxide mediated by .gamma.-IFN in mouse peritoneal macrophage was increased by antisense-TGF.betha. in a dose-dependent manner. Antisense-$TGF{\beta}$ reduced the nitric oxide release from activated RAW 264.7 cells. Significant enhancement in the nitric oxide production was investigated by the cotreatment of poly-L-lysine with antisense-$TGF{\beta}$On the meanwhile, inhibition effect of antisense-$TGF{\beta}$ is not changed by the addition of poly-L-lysine. These results demonstrate that control of expression of $TGF{\beta}$ and TNF.alpha. gene is achieved using antisense technology and the cellular uptake of antisense oligonucleotide could be enhanced by ion-pairing.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.140-153
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• 2003

Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

• Archives of Pharmacal Research
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• v.21 no.2
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• pp.120-127
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• 1998

Peroxisome proliferators induce hepatic peroxisome proliferation and hepatic tumors in rodents. These chemicals increase the expression of the peroxisomal $\beta$-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including eicosanoids. Peroxisome proliferators transiently induce increased cell proliferation in vivo. However, peroxisome proliferators are weakly mitogenic and are not co-mitogenic with epidermal growth factor (EGF) in cultured hepatocytes. Earlier study found that the peroxisome proliferator ciprofibrate is cornitogenic with eicosanoids. In order to study possible mechanisms of the comitogenicity of peroxisome proliferator ciprofibrate and eicosanoids' we hypothesized that the co-mitogenicity may result from synergistic or additive increases of second messengers in mitogenic signal pathways. We therefore examined the effect of the peroxisome proliferator ciprofibrate, prostaglandin $F_2_{\alpha}$($PGF_2{\alpha}$) and the combination of ciprofibrate and $PGF_2{\alpha}$ with or without growth factors on the protein kinase C (PKC) activity, and inositol-1, 4, 5-triphosphate ($IP_{3-}$) and intracellular calcium ($[Ca^{2+}]_i$) concentrations in cultured rat hepatocytes. The combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased particulate PKC activity. The combination of ciprofibrate and $PGF_2{\alpha}$ also significantly increased EGF, transforming growth factor-$\alpha$ ($TGF_2{\alpha}$) and hepatic growth factor (HGF)-induced particulate PKC activity. The combination of ciprofibrate and $PGF_2_\alpha$greatly increased $[Ca^{2+}]_i$. However, the increases of PKC activity and $[Ca^{2+}]_i$ by ciprofibrate and $PGF_2{\alpha}$ alone were much smaller. Neither ciprofibrate or $PGF_2{\alpha}$ alone nor the combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased the formation of $IP_3$. The combination of ciprofibrate and $PGF_2{\alpha}$, however, blocked the inhibitory effect of $TGF-{\beta}$ on particulate PKC activity and formation of $IP_3$ induced by EGF. These results show that co-mitogenicity of the peroxisome proliferator ciprofibrate and eicosanoids may result from the increase in particulate PKC activity and intracellular calcium concentration but not from the formation of $IP_3$.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.1-12
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• 1999

Bacterial infection of the pulp results in the development of a periapical lesion with the concomitant resorption of periapical bone. The cytokines are believed to play an important role in this matter. The purpose of this study was to find the relationship among the presence of black pigmented bacteria, the levels of cytokines(TNF-${\alpha}$, -${\beta}$, IL-$1{\beta}$, and TGF-${\beta}1$), and the amount of bone resorption in periapical and pulpal diseases. For the purpose, the patients were grouped into chronic apical pathosis, acute apical pathosis, acute pulpitis, and a healthy control group. Root canal samples were taken from periapical tissue exudates during routine endodontic treatment, and the venous blood was taken from each patients. The samples were processed to measure local and systemic levels of the cytokines using enzyme linked immunosorbent assay(ELISA). Bacterial content of Porphyromonas endodontalis, Porphyromonas gingivalis, and Prevotella nigrescens were measured by indirect immunofluorescence method and the size of the periapical lesions were measured from the radiographs. The following results were obtained: 1. The levels of bone resorptive cytokines(TNF-${\alpha}$, TNF-${\beta}$, and IL-$1{\beta}$) in exudates from acute and chronic apical pathoses were significantly higher than those from acute pulpitis and the normal pulps(p<0.05). 2. IL-$1{\beta}$ were the highest among the bone resorptive cytokines in apical pathoses. However, no statistical difference between acute and chronic lesions were found(p>0.05). 3. The levels of TGF-${\beta}1$ in exudates from acute pulpitis and chronic apical pathoses were significantly higher than those from acute apical pathoses and the normal pulps(p<0.05). However, there were no significant correlations among the levels of bone resorptive cytokines. 4. The levels of TNF-${\beta}$ in serum were significantly higher than those from the exudates while serum TGF-${\beta}1$ concentrations were significantly lower(p<0.05). 5. Exudates from the canals in which the P. nigrescens were detected showed significantly higher levels of IL-$1{\beta}$ than those from the canals without the microorganism(p<0.05). 6. There were no significant correlations among the levels of the cytokines, the amount of bone destruction, and the presence of acute and chronic symptoms(p>0.05).

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.807-815
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• 2011

This study was designed to investigate the effects of Mokhyangjoki-san extract (MJS) on the improvement in cerebral blood flow (rCBF) in cerebral ischemic rats, and further to determine cytokines production (IL-1${\beta}$, TNF-${\alpha}$, IL-10, TGF-${\beta}$) of MJS. The results in cerebral ischemic rats were as follows ; The rCBF was significantly and stably increased by MJS (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, MJS 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 after reperfusion, MJS significantly decreased IL-1${\beta}$ and TNF-${\alpha}$ production compared with control group. IL-10 and TGF-${\beta}$1 production in MJS group were significantly increased compared with control group. These results suggested that MJS significantly and stably increased rCBF by inhibiting the production IL-1${\beta}$ and TNF-${\alpha}$, and accelerating that of IL-10 and TGF-${\beta}$. The result in nerve cells was as follows ; MJS significantly inhibited lactate dehydrogenase activity in vitro in a dose-dependent manner. This result suggested that MJS prevented the neuronal death.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2004.07a
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• pp.32-32
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• 2004

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1585-1587
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• 2008

Fibroblast is constantly subjected to mechanical loads in connective tissues where mechanical signals are converted to intercellular biochemical events. The aim of this study is to understand the effects of tensile stress on the neurotrophin (NT) and transforming growth factor (TGF) expression of fibroblast in vitro. Nerve growth factor (NGF) stimulates fibroblast migration, and TGF is related to tissue repair. In this study, at the uniaxial stretch of 10% strain and frequency of 0.5 Hz, different resting times of 0, 20, and 60 min are placed in between 10 min stimulations periods. Results show increase in NGF mRNA levels and a substantial decrease in NT3 mRNA after 1 hr of stimulation, indicating that the tensile stress may regulate NGF and NT3, key factors for the neurocosmetic applications. The mRNA level for TGF-${\alpha}$ and TGF-${\beta}2$ had increased up to two-folds after 1 hr of stimulation, showing that the tensile stress may control TGF, an important part of wound healing.

• Food Science of Animal Resources
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• v.32 no.3
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• pp.339-345
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• 2012

This experiment was carried out in order to separate bovine colostral whey protein from Imsil province and to test the effect of immunological activity on RAW 264.7 cells. The colostral whey protein contained TGF-${\beta}$ 7, 475 pg/g in total. We first tested the effect of the colostral whey protein on the proliferation of RAW 264.7 cells and it demonstrated cytotoxicity at concentrations greater than 20 mg/mL. Therefore, the immunological activities of colostral whey protein were investigated in maximum concentration of 10 mg/mL on LPS-induced RAW 264.7 cells. Results indicated that colostral whey protein inhibited the LPS-induced nitric oxide (NO) production in a dose-dependent manner. The colostral whey protein also suppressed the productions of proinflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in a dose-dependent manner. In addition to the immunological activity, colostral whey protein led to the expression of heme oxygenase-1 (HO-1) in RAW 264.7 cells. In conclusion, colostral whey protein containing TGF-${\beta}$ inhibited the production of NO, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 via expression of HO-1.