• The korean journal of orthodontics
• /
• v.30 no.6 s.83
• /
• pp.713-721
• /
• 2000

Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.4
• /
• pp.871-888
• /
• 1997

Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

• Parasites, Hosts and Diseases
• /
• v.50 no.4
• /
• pp.301-308
• /
• 2012

In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of $CD19^+$ B cells was observed as early as week 1 post-infection while $CD4^+/CD8^+$ T cells were down-regulated. Accumulation of $Mac1^+$ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-${\alpha}$ mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-$1{\beta}$ expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-${\beta}$ were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-${\beta}$ and IL-4 during the early stages of infection.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8143-8147
• /
• 2014

To investigate the expression intensity and prognostic significance of TGF-${\beta}1$ protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-${\beta}1$ protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-${\beta}1$ PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-${\beta}1$ protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000,). Multivariate analysis showed that TGF-${\beta}1$ protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p=0.030) were also independent prognostic factors. Thus, TGF-${\beta}1$ protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.

• The Journal of Korean Physical Therapy
• /
• v.14 no.4
• /
• pp.87-94
• /
• 2002

Low intensity laser irradiation is potential physical agent that triggers the muscle regeneration by previous study. In muscle regeneration, a number of growth factors also promotes that is triggered in response to muscle damage. The transforming growth factor(TGF)-$\beta$ is involved in the activation of cell proliferation and the inhibition of cell differentiation in muscle regeneration. This is secreted not only autocrine system but also paracrine and endocrine. Therefore, We investigated that effects of Gallium aluminum arsenide(GaAlAs) diode laser for the expression of TGF-$\beta$ on lumbar spinal cord after extensor digitorum muscle crush injury. After laser irradiation, the immunoreactivity of TGF-$\beta$ was increased bilaterally in gray mater of spinal cord. Especially, in 1 day, experimental group was highed than control, and in 3 day, lateral motor nucleus were storong immunoreactivy of TGF-$\beta$. Also, in 1 and 2 day, TGF-$\beta$ was showed in white mater as well as gray mater, but in 3 day, only showed in gray mater. These data may suggests to the establishment of laser irradiation on spinal cord for skeletal muscle injury.

• Development and Reproduction
• /
• v.11 no.1
• /
• pp.43-47
• /
• 2007

Smad proteins mediate transforming growth $factor(TGF)-{\beta}$ signaling and play a pivotal role in embryonic development. The estrogen receptor-related receptors(ERRs), which are structurally similar to estrogen receptors, are members of orphan nuclear receptor in the nuclear receptor superfamily and their functions are known to be involved in the formation of extra-embryonic ectoderm. To investigate the involvement of Smad3 and $ERR{\beta}$ like 1 in reproductive activities and embryogenesis in marine invertebrate, we examined gene expression of Smad3 and $ERR{\beta}$ like 1 in Strongylocentrotus nudus during their seasonal changes and embryonic development using real-time polymerase chain reaction. The Smad3 mRNA levels in gonad showed an increasing pattern from February to June 2004 but decreased at August(spawning season) followed by an elevation of the levels at October and December 2004. The mRNA levels of the $ERR{\beta}$ like 1 significantly elevated during the spawning season. During embryonic development, Smad3 mRNA levels at $8{\sim}16$ cell stages were significantly higher than those of other stages, whereas the mRNA of the $ERR{\beta}$ like 1 was significantly high levels at late development stages, i.e., blastular, gastrula and plutei stages. These results suggest that the Smad3 could be involved at least in part in the early cleavage stages and the $ERR{\beta}$ like 1 may play an important role in the spawning season and late developmental stage in the sea urchin.

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

• Development and Reproduction
• /
• v.15 no.2
• /
• pp.99-111
• /
• 2011

The present experiment was performed to evaluate the chondrogenic differentiation potential of human adipose tissue-derived mesenchymal stem cells (ATMSCs) in the chondrogenic induction medium (CIM) with transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and to evaluate the chondrogenic differentiation of ATMSCs seeded in gelatin-chondroitinglucosamine scaffold (GCG-scaffold). ATMSCs and mouse chondrocytes were cultured in the basic medium and CIM without TGF-${\beta}1$ (CIM1) or with TGF-${\beta}1$ (CIM2) for chondrogenic differentiation potential. The chondrogenic differentiation of ATMSCs was evaluated by glycosaminoglycan (GAG) synthesis and histochemical staining. In pellet culture, GAG synthesis of ATMSCs and chondrocyte was increased in culture on 14 days, but higher in CIM1 than basic medium, especially highest in CIM2. Cartilage matrix was observed in ATMSCs cultured in CIM2 on 14 days by Safranin O and trichrome staining. In well plate culture, proliferation of ATMSCs was continuously increased in culture on 10 days and higher in CIM than basic medium. The cell adhesion rate of ATMSCs seeded in flask or scaffolds was continuously increased during culture period, but higher in scaffold than flask. GAG synthesis of ATMSCs seeded in scaffolds showed no change in control group. In the CIM groups, GAG synthesis of ATMSCs was continuously increased than control group during culture period, especially very high in CIM2 and in the GCG-scaffold was slightly higher than the gelatin scaffold (G-scaffold). The present results demonstrated that ATMSCs showed an low chondrogenic differentiation potential, compared to mouse chondrocytes for 14 days of culture. TGF-${\beta}1$ is important factor in chondrogenic differentiation of ATMSCs. Gelatin scaffold was considered to increasing the effective chondrogenic differentiation environment. ATMSCs seeded in GCG-scaffold was more effective in chondrogenesis than in G-scaffold. Conclusively, the present results demonstrated that the treatment of chondroitin and glucosamine in the scaffold was more effective to promote the cartilage matrix formation.

• Journal of Periodontal and Implant Science
• /
• v.32 no.3
• /
• pp.457-473
• /
• 2002

The purposes of this study is to evaluate the combination effects of TGF-${\beta}_1$ and PDGF-BB on the periodontal ligament cells to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM/100% FBS at the $37^{\circ}C$, 5% $CO_2$ incubator. Authors measured the DNA synthesis, total protein, collagen and noncollagenous protein synthesis according to the concentration of TGF-${\beta}_1$,(1,5ng/ml) and PDGF-BB (1,10 ng/ml) in combination. To explore further this delayed effect of TGF-${\beta}_1$, we preincubated human periodontal ligament cells with TGF-${\beta}_1$ for 4 or 24 hours before PDGF-BB stimulation. The results were as follows: The DNA synthetic activity was increased dose dependently by TGF-${\beta}_1$, PDGF-BB. The combination of TGF-${\beta}_1$ and PDGF-BB consistently enhanced the DNA synthetic activity to PDGF-BB alone. The ability of TGF-${\beta}_1$ to enhance DNA synthetic activity in PDGF-BB treated periodontal ligament cells was dose dependent. The maximum mitogenic effect was at the 5ng/ml of TGF-${\beta}_1$ and l0ng/ml of PDGF-BB. Preincubation of cell with TGF-${\beta}_1$ resulted in significantly greater response to PDGF-BB at all TGF-${\beta}_1$ concentration studied, and may be useful for clinical application in periodontal regenerative procedures. The total protein, collagen and noncollagen synthesis was increased dose pendently by TGF-${\beta}_1$, PDGF-BB. The % of collagen was slightly decreased according to the concentration of TGF-${\beta}_1$, PDGF-BB. The effect of TGF-${\beta}_1$, PDGF-BB were not specific for collagen synthesis since it also increased noncollagenous protein synthesis. This study demonstrates that PDGF-BB is major mitogens for human periodontal ligament cells in vitro, and supports a role for TGF-${\beta}_1$ as a regulation of the mitogenic and total protein formation to PDGF-BB in these cells.

• The Journal of Internal Korean Medicine
• /
• v.35 no.4
• /
• pp.519-531
• /
• 2014

Objectives: Diabetic nephropathy is the most common cause of end stage renal disease. Transforming growth factor (TGF)-${\beta}1$, type IV collagen, advanced glycation end-products (AGEs), and angiotensin II type 1 receptor (AT1) are the main factors of diabetic nephropathy. We investigated the effects of Prunus on renal function and histopathological changes of diabetic nephropathy rat model induced by unilateral nephrectomy and streptozotocin. Methods: Diabetes was induced in male Sprague-Dawley rats ($290{\pm}10g$) by injecting streptozotocin (55 mg/kg) into the tail vein after unilateral nephrectomy. Rats were divided into 3 groups (n=6): normal, control, and Prunus. After 8 weeks of oral administration of Prunus extract on the Prunus group from 3 days after streptozotocin injection, we checked weight, 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, low density lipoprotein (LDL), triglyceride, TGF-${\beta}1$, type IV collagen, AGEs, and AT1. We also measured mRNA expression of TGF-${\beta}1$, type IV collagen, AGEs, and AT1 by Real Time polymerase chain reaction (RT-PCR). Results: Prunus decreased the amount of 24 hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of TGF-${\beta}1$, type IV collagen and AGEs which could promote development of diabetic nephropathy. Prunus also inhibited mRNA expression of TGF-${\beta}1$, type IV collagen. Conclusions: These findings suggest that Prunus might protect the renal function and inhibit the development of renal injury by regulating factors including TGF-${\beta}1$, type IV collagen, AGEs, except AT1, so Prunus can be used for diabetic patients to prevent the progression of diabetic nephropathy.