• 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.

• BMB Reports
• /
• v.56 no.3
• /
• pp.196-201
• /
• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Restorative Dentistry and Endodontics
• /
• v.48 no.1
• /
• pp.6.1-6.14
• /
• 2023

Objectives: This study evaluated the effects of high-plasticity mineral trioxide aggregate (MTA-HP) on the activity of M1 and M2 macrophages, compared to white MTA (Angelus). Materials and Methods: Peritoneal inflammatory M1 (from C57BL/6 mice) and M2 (from BALB/c mice) macrophages were cultured in the presence of the tested materials. Cell viability (MTT and trypan blue assays), adhesion, phagocytosis, reactive oxygen species (ROS) production, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β production were evaluated. Parametric analysis of variance and the non-parametric Kruskal-Wallis test were used. Results were considered significant when p < 0.05. Results: The MTT assay revealed a significant decrease in M1 metabolism with MTA-HP at 24 hours, and with MTA and MTA-HP later. The trypan blue assay showed significantly fewer live M1 at 48 hours and live M2 at 48 and 72 hours with MTA-HP, compared to MTA. M1 and M2 adherence and phagocytosis showed no significant differences compared to control for both materials. Zymosan A stimulated ROS production by macrophages. In the absence of interferon-γ, TNF-α production by M1 did not significantly differ between groups. For M2, both materials showed higher TNF-α production in the presence of the stimulus, but without significant between-group differences. Likewise, TGF-β production by M1 and M2 macrophages was not significantly different between the groups. Conclusions: M1 and M2 macrophages presented different viability in response to MTA and MTA-HP at different time points. Introducing a plasticizer into the MTA vehicle did not interfere with the activity of M1 and M2 macrophages.

• The Journal of Korean Medicine
• /
• v.27 no.4
• /
• pp.1-11
• /
• 2006

Objectives : We investigated the effect of Dohongsamul-tang (DHSMT) on the production of various cytokines in lipopolysaccaride (LPS) stimulated peripheral mononuclear cells (PBMCs) from CI patients. Methods: Cell viability was determined using MTT assay. ELISA was carried out for investigating $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, IL-8, IL-4, and $TGF-{\beta}$ 1 Results : The amount of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, IL-8, IL-4, and transforming growth factor(TGF)-${\beta}$ 1 in PBMC culture supernatant significantly increased in the LPS treated cells compared to unstimulated cells. We show that DHSMT inhibited the production of TNF-${\alpha}$, IL-1${\beta}$, IL-6, IL-8, and IL-4 induced by LPS in a dose dependent manner. The maximal inhibition rate of the TNF-${\alpha}$, IL-1${\beta}$, IL-6, IL-8, and IL-4 production by pretreatment of DHSMT (1.0mg/ml) was 38.52 ${\pm}$ 2.5% (P < 0.01), 44.02 ${\pm}$ 3.5% (P < 0.05), 45.32 ${\pm}$ 2.3% (P < 0.01), 42.30 ${\pm}$ 3.1% (P < 0.05), and 49.70　${\pm}$　3.1%(P ＆lt; 0.05), respectively. On the other hand, DMSMT significantly increased the LPS-induced TGF-${\beta}$ 1 production(P<0.05). Conclusions : Taken together. these results suggest that DHSMT might have regulatory effects on cytokine production, which might explain its beneficial effect in the treatment of CI.

• Journal of Korean Medicine Rehabilitation
• /
• v.28 no.1
• /
• pp.1-17
• /
• 2018

Objectives The purpose of this study was to evaluate the effect of Jeopgolsan (JGS) extract on anti-oxidant, anti-inflammatory activities in RAW 264.7 cells and on factors related with fracture healing in skull fractured rat. Methods Experimental animals were divided into four groups: normal group without any treatment (Normal), contral group were treated orally with distilled water (Control), Experimental group were treated orally with JGS at a concentration of 200 mg/kg/day (JGS 200) and Experimental group were treated orally with JGS at a concentration of 200 mg/kg/day (JGS 400). Rats in each group except the normal group were induced fractures in the skull. The 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity were measured to evaluate antioxidant activity. The production of nitric oxide (NO), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in the RAW 264.7 cells were measured to evaluate anti-inflammatory activity. The production of osteocalcin calcitonin, carboxy-terminal telepeptides of type II collagen (CTX II), transforming growth $factor-{\beta}$ ($TGF-{\beta}$), bone morphogenetic protein-2 (BMP-2), Insulin and alkaline phosphatase (ALP) in serum of rats were measured to evaluate the effects of fracture healing at 0, 2, 4, and 6th week. X-rays were taken every 3 week from 0 to 6th week to evaluate fracture healing effect. Results 1. No cytotoxicity was observed. 2. DPPH and ABTS radical scavenging activity were increased in a concentration dependent manner, indicating anti-oxidant effect. 3. NO, $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ were not significantly changed, indicating no anti-inflammatory effect. 4. Osteocalcin, Calcitonin, $TGF-{\beta}$ and ALP were significantly increased in the experimental groups. 5. CTX II, insulin were significantly decreased in the expermental groups. 6. Radiologic examination showed that union of fracture was promoted. Conclusions From above results, JGS showed significant results in factors related with fracture healing and radiologic examination. Threfore, JGS is expected to be effective in the treatment of fracture.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.28 no.3
• /
• pp.169-174
• /
• 2002

Purpose: Irradiation in the oral cancer patients causes early and late complications such as intraoral mucositis and fibrosis, with a various expression of GM-CSF and TGF-${\beta}1$. The purpose of this study was to investigate the production of GM-CSF and TGF-${\beta}1$ by the irradiated human gingival fibroblasts cultivated with lipopolysaccharide. Materials and Methods: Irradiated (total dose, 60 Gy) human gingival fibroblasts were incubated with LPS. Culture supernatants that were collected at 24, 48, and 72 hours were assessed for GM-CSF and TGF-${\beta}1$ by enzyme-linked immunosorbent assay. Results: 1. GM-CSF production in nomal gingival fibroblasts was increased with incubation time, but decreased with incubation time in irradiated gingival fibroblasts. GM-CSF production in both normal and irradiated gingival fibroblasts induced with LPS was higher than the control. 2. TGF-${\beta}1$ production in normal gingival fibroblasts was decreased after 24 hours, but, it was increased until 48 hours in irradiated gingival fibroblasts. TGF-${\beta}1$ production in normal gingival fibroblasts exposed with LPS was higher than the control. Conversely, It was lower than the control in irradiated gingival fibroblasts exposed with LPS. Conclusion: This indicates that irradiation in gingival fibroblasts may play an important role in radiation-induced intraoral mucositis and fibrosis. However, LPS decreases the production of TGF-${\beta}1$ in the irradiated gingival fibroblasts.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.1
• /
• pp.54-63
• /
• 2010

Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

• Journal of Life Science
• /
• v.33 no.12
• /
• pp.1062-1073
• /
• 2023

Although depression is a common psychiatric disorder that negatively affects individuals and societies, its exact pathogenesis is not well understood. Stress is a major risk factor for depression and is known to increase susceptibility by triggering inflammation. Indeed, many preclinical and clinical studies have suggested a strong link between depression and inflammation. Depression is associated with increased levels of pro-inflammatory cytokines, such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor-α, and interferon-γ, and decreased levels of the anti-inflammatory IL-4, IL-10, and transforming growth factor-β. Administering pro-inflammatory cytokines causes depression-like behaviors in rodents. Conversely, administering anti-inflammatory drugs appears to ameliorate depressive symptoms. Although the importance of inflammation as a mediator of depression has been demonstrated, the mechanisms by which inflammation is activated in depression remain unclear. To address this issue, recent studies have focused on the importance of stress-induced sterile inflammation. Sterile inflammation refers to the activation of inflammatory processes due to physical and/or psychological stress in the absence of pathogens. Stress promotes the release of endogenous factors known as damage-associated molecular patterns (DAMPs), thereby triggering sterile inflammation. In turn, DAMPs are recognized by pattern recognition receptors, leading to the production of pro-inflammatory cytokines. Here, we review the role of DAMPs in depression based on preclinical and clinical evidence on the dysregulation of sterile inflammation.

• Journal of Animal Science and Technology
• /
• v.63 no.5
• /
• pp.1076-1085
• /
• 2021

The study was conducted to evaluate the effects of spray-dried plasma (SDP) supplementation during late gestation and lactation on productive performance and immune responses of sows and their litters. Twelve sows (227.78 ± 2.16 kg average body weight; 2.0 average parity) were randomly allotted to two dietary treatments: a basal diet (CON) and the basal diet supplemented with 1% SDP. Sows were fed experimental diets from d 30 before farrowing to weaning of their piglets. Blood samples were collected from sows on d 1, 3, and 7 of lactation and from two randomly selected nursing pigs per litter on d 3 and 7 after birth, and d 1, 3, and 7 after weaning. Productive performance and immune responses of sows and their piglets were measured. There was a trend of less body weight loss in sows supplemented with SDP (p < 0.10) during the lactation period and a trend of greater (p < 0.10) average daily gain in SDP piglets compared to those in the CON group. Sows in the SDP group tended to have lower (p < 0.10) serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and cortisol on d 3 and lower serum concentration of TNF-α on d 7 compared with sows in CON group. In comparison with CON piglets, piglets from SDP sows tended to have lower (p < 0.10) serum concentrations of TNF-α, TGF-β1, and cortisol on d 7 after birth, lower (p < 0.10) serum TNF-α and C-reactive protein on d 3 and 7 after weaning, and greater (p < 0.10) average daily gain after weaning. Moreover, weaned pigs from sows fed SDP had significantly lower (p < 0.05) serum concentrations of cortisol and TGF-β1 on d 3 and 7 postweaning, respectively, than CON piglets. In conclusion, SDP supplementation in sow diets from late gestation to weaning improved the productive performance of sows and their offspring; the beneficial effects of SDP may be mediated in part through modulation of immune responses of both sows and piglets.

• BMB Reports
• /
• v.34 no.1
• /
• pp.80-84
• /
• 2001

The human papillomavirus E7 protein can form a specific complex with a retinoblastoma tumor suppressor gene product (p105-Rb) that results in the release of the E2F transcription factor, which is critical for the growth-deregulation and transforming properties of the viral E7 oncoprotein. In an attempt to apply interaction between the E7 oncoprotein and a target cellular protein Rb for an in vitro screening system for drugs against human papillomavirus infection, we primarily investigated the E7Rb binding through a pull down assay and enzyme-linked immunosorbent assay. The pull down assay showed that both glutathione S-transferase-tagged E7 and His-tagged E7 immobilized on resins specifically produced complexes with bacterially expressed Rb in a dose-dependent manner, as determined by immunoblot analyses. This result coincided with that of an enzyme-linked immunosorbent assay, which is a useful system for the mass screening of potential drugs. Taken together, this screening system (based on the interaction between E7 and Rb) can be a promising system in the development of drugs against cervical cancers caused by human papillomavirus infection.