• Korean Journal of Biological Psychiatry
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• v.13 no.1
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• pp.32-37
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• 2006

Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

• Journal of the Korean Magnetic Resonance Society
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• v.24 no.1
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• pp.1-8
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• 2020

An extracellular matrix protein, transforming growth factor-beta-induced protein (TGFBIp/βig-h3), which is induced by transforming growth factor-β in the human cornea, skin, and matrix of many connective tissues, is associated with the adhesion, migration, proliferation, and differentiation of various cells. TGFBIp contains four homologous repeat domains, known as FAS1 domains, where certain mutations have been considered to cause corneal dystrophies. In this study, backbone NMR assignments of FAS1-3/FAS1-4 tandem domain were obtained and compared with those previously known for the isolated FAS1-4 domain. The results corroborate in solution the inter-domain interaction between FAS1-3 and FAS1-4 in TGFBIp.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• Laboraroty Animal Research
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• v.33 no.2
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• pp.76-83
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• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.124-131
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• 2021

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

• KSBB Journal
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• v.19 no.5
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• pp.335-340
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• 2004

Mesangial expansion caused by cell proliferation and glomerular extracellular matrix accumulation is one of the earliest renal abnormalties observed at the onset of hyperglycemia in diabetes mellitus. Transcription factor Sp1 is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation, and is assumed to play an essential role in mesangial expansion, transforming growth factor (TGF)-$\beta$1, plasminogen activator inhibitor (PAI)-1. We have generated a phosphorothioated double-stranded Sp1-decoy oligodeoxynucleotide that effectively blocks Sp1 binding to the promoter region for transcriptional regulation of TGF-$\beta$1 and PAI-1. The Sp1 decoy oligodeoxynucleotide suppressed transcription of these cytokines and proliferation of primary rat mesangial cells in response to serum stimulation. These results suggest that the Sp1 decoy oligodeoxynucleotide could bea powerful tool in preventing the pathogenesis of renal hypertrophy.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.805-809
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• 2006

Background: In our previous study, we demonstrated that transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) may have a role in the formation of bullae. In this study, we investigated if expression of transforming growth factor-beta 1 (TGF-${\beta}1$) ligand was altered in a bullous lung tissue by immunohistochemical staining of bullous tissues from patients with primary spontaneous pneumothorax. Material and Method: Bullous lung tissues were obtained from 36 patients with primary spontaneous pneumothorax, including 34 males and 2 females aged 14 to 38 years old. Result: Of the 36 patients, 19 were TGF-${\beta}1$ positive and 24 were transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) positive. Among the 19 TGF-${\beta}1$ positives, 15 were also TGF-${\beta}1RII$ positive, observation at high magnification showed that strong immunohistochemical stain was detected in the boundary region between the bullous and normal lung tissues. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ may be involved in the formation of a bulla as well as the alteration of TGF-${\beta}1RII$ expression. Further molecular studies are needed to elucidate the more detailed molecular mechanisms of the bulla formation.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.143-150
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• 2005

Background:Several reports have suggested that cytokine alterations could be related to the pathophysiology of schizophrenia. In this study, we measured plasma level of interleukin-12(IL-12), a proinflammatory T helper 1(Th1) cytokine and transforming growth factor-${\beta}1$(TGF-${\beta}1$), an anti-inflammatory Th3 cytokine before and after antipsychotic treatment in schizophrenic patients. Methods:The plasma concentrations of IL-12 and TGF-${\beta}1$ were measured by using quantitative ELISA in 23 schizophrenic patients and 31 normal controls at admission and 8 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS). Results:IL-12 and TGF-${\beta}1$ levels were significantly higher in schizophrenic patients than in controls before treatment. At the 8 week of treatment, the TGF-${\beta}1$ levels returned to control values, while IL-12 levels were not significantly changed. There were no significant correlations between the changes of BPRS scores and the changes of IL-12 or TGF-${\beta}1$ levels in schizophrenic patients. Conclusion:Cytokine abnormalities in schizophrenia might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}1$ plays an important role in the schizophrenia.