• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.5
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• pp.444-450
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• 2005

Epidermal growth factor (EGF) activates many intracellular effector molecules, which subsequently influence the expression levels of many genes involved in cell growth, apoptosis and signal transduction, etc. In this study, the early response of gene expressions due to EGF treatment was monitored using oligonucleotide DNA microarrays in rat schwannoma cell lines. An immunoblotting experiment showed the successful activation of EGF receptors and an effector protein, STAT5, due to EGF treatment. The microarray study showed that 35 genes were significantly induced and 2 were repressed within 60 min after the treatment. The list of induced genes included early growth response 1, suppressor of cytokine signaling 3, c-fos, interferon regulatory factor 1 and early growth response 2, etc. According to the microarray data, six of these were induced by more than 10-fold, and showed at least two different induction patterns, indicating complicated regulatory mechanisms in the EGF signal transduction.

• Biomedical Science Letters
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• v.13 no.2
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• pp.157-160
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• 2007

Endoplasmic reticulum (ER) plays formation of disulfide bonds and proper folding of secretory proteins. Cellular responses to ER stress enhances the stress-activated kinase pathway and the induces a lot of immediate-early genes. Among of them, the early growth response-1 (Egr-1), a transcription factor, which plays an important role in cell growth, development, differentiation, apoptosis and various types of injury. For that reason, we have tested the expression of Egr-1 against ER stress inducible drugs (tunicamycin, DTT, A23187 and BFA) to understand what kind of aspect occurred by ER stresses.

• Journal of dental hygiene science
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• v.19 no.4
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• Journal of Periodontal and Implant Science
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• v.47 no.2
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• pp.106-115
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• 2017

Purpose: The possibility of immediate or early loading has become popular in implant dentistry. A prerequisite for the immediate or early loading of an implant prosthesis is the achievement of initial stability in the implant. Moreover, in response to clinicians' interest in verifying clinical stability to determine the optimal time point for functional loading, a non-invasive method to assess implant stability has been developed on the basis of resonance frequency analysis (RFA). The primary objective of this study was to monitor the stability of sandblasted, large-grit, and acid-etched (SLA) implants with different diameters during the early phases of healing by RFA. The secondary objective was to evaluate how the initial stability of implants varied depending on different surface modifications and other contributing factors. Methods: Thirty-five implants (25 SLA implants and 10 resorbable blasting media [RBM] implants) placed in 20 subjects were included. To measure implant stability, RFA was performed at baseline and at 1, 2, 3, 4, 6, and 10 weeks after surgery. Results: The longitudinal changes in the implant stability quotient (ISQ) values were similar for the SLA implants with different diameters and for the RBM implants. During the initial healing period, the ISQ decreased after installation and reached its lowest values at 1 week and 2 weeks, respectively. The mean ISQ values in the SLA implants were significantly higher in ${\varnothing}5.0mm$ implants than in ${\varnothing}4.0mm$ implants. Men showed a higher ISQ than women. Mandibular sites showed a higher ISQ than maxillary sites. Conclusions: All implants used in this study are suitable for immediate or early loading under appropriate indications. A wider diameter and SLA surface treatment of implants could improve the stability, if the implant is fixed with at least 30 Ncm of insertion torque.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.17-20
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• 1993

As a step toward a more complete understanding of the molecular actions of TNF, we prepared a cDNA library from TNF-treated human FS-4 fibroblasts and used differential hybridization to identify cDNA clones corresponding to mRNAs enriched in TNF-treated eells. In Quiescent FS-4 cells n induces an increase in the level of some mRNAs within 20 to 30 min. Some of these immediate-early response mRNAs are elevated only transiently for about 30 to 120 min, e. g., c-fos and c-myc (Lin and Vilcek,1987) or the transcription factor IRF-1 (Fujita et al.1989). Such immediate-early gene products may be important for the activation of other genes, but their transient induction suggests that they are not the actual effector molecules responsible for the phenotypic changes induced by TNF. We chose a 3-h incubation with W because we were seeking cDNAs corresponding to messages that are more stably elevated after TNF treatment. Indeed, the results shown in Figure 8 and 9 indicate that all of the mRNAs corresponding to the eight TSG cDNAs isolated remained significantly elevated after 16h of continuous treatment with TNF, and their kinetics of induction were clearly different from those of the immediate-early response mRNAs such as c-fos, c-myc or IRF-1. Nevertheless, only the induction of TSG-21 (collagenase) and TSG-27 (stromelysin) nNAs was completely inhibited by cycloheximide and the induction of TSG-37 (metallothionein-II) was reduced in the presence of this inhibitor of protein synthesis. Induction of the other five TSG mRNAs by TNF was completelyresistant to cycloheximide, suggest ins that no protein intermediate is needed for the upregulation of these mRNAs.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.461-465
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• 2015

Microglia, the resident macrophages in the central nervous system, can rapidly respond to pathological insults. Toll-like receptor 2 (TLR2) is a pattern recognition receptor that plays a fundamental role in pathogen recognition and activation of innate immunity. Although many previous studies have suggested that TLR2 contributes to microglial activation and subsequent pathogenesis following brain tissue injury, it is still unclear whether TLR2 has a role in microglia dynamics in the resting state or in immediate-early reaction to the injury in vivo. By using in vivo two-photon microscopy imaging and $Cx3cr1^{GFP/+}$ mouse line, we first monitored the motility of microglial processes (i.e. the rate of extension and retraction) in the somatosensory cortex of living TLR2-KO and WT mice; Microglial processes in TLR2-KO mice show the similar motility to that of WT mice. We further found that microglia rapidly extend their processes to the site of local tissue injury induced by a two-photon laser ablation and that such microglial response to the brain injury was similar between WT and TLR2-KO mice. These results indicate that there are no differences in the behavior of microglial processes between TLR2-KO mice and WT mice when microglia is in the resting state or encounters local injury. Thus, TLR2 might not be essential for immediate-early microglial response to brain tissue injury in vivo.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.5
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• pp.424-430
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• 2005

The oral cavity is humid environment mainly due to the continuous salivary flow. The reaction of oral mucosa to fluid flow is important for homeostasis and pathogenesis. The objective of this study is the screening the change of gene expression after the application of fluid induced shear stress (FISS) on the gingival fibroblast using cDNA microarray assay. The immortalized human gingival fibroblasts were grown and FISS was applied using a cone viscometer at a rotational velocity of 40 rpm, respectively for periods of 2 and 4 hours. The synthesis of cDNA was done from the extracted total RNA and cDNA microarray assay was done subsequently. The genes that showed over 1.6 in the Cy3/Cy5 or the Cy5/Cy3 value were regarded as genes influenced significantly by the FISS application ion (/M/>0.7). The " RUNX-1" was increased its expression in 2 hours group and " RUN and SH3 domain containing 1" was increased its expression in 4 hours group. The "CC020415", "cyclin L1", "interferon regulatory factor1", "early growth response 1", "immediate early response 2", and "immediate early response 3" genes were increased their expression in 2 and 4 hours after FISS application. In conclusion, we could find many genes that were probably related to the FISS application. Interestingly, most of them were placed in similar molecular pathways and these findings improve the reliability of chip data and usefulness in overall screening. From this experiment, we could find many items for further study and it will make improvement in the understanding of intracellular events in response to FISS.

• 대한생식의학회:학술대회논문집
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• 2006.06a
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• pp.154.1-154.1
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• 2006

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.679-682
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• 2015

Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC.

• Journal of dental hygiene science
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• v.19 no.3
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• pp.198-204
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• 2019

Background: Oxidative stress is a known to be associated with in the pathogenesis of many inflammatory diseases, including periodontitis. Ursolic acid is a pentacyclic triterpenoid with has antimicrobial, antioxidative, and anticancer properties. However, the role of ursolic acid in the regulating of osteogenesis remains undetermined. This study was aimed to elucidate the crucial osteogenic effects of ursolic acid and its ability to inhibit oxidative stress by targeting the immediate early response 3 (IER3)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Methods: Cell proliferation was determined using water-soluble tetrazolium salt assay, cell differentiation was evaluated by alkaline phosphatase (ALP) activity, and formation of calcium nodules was detected using alizarin red S stain. Generation of reactive oxygen species (ROS) was determined using by DCFH-DA fluorescence dye in hydrogen peroxide ($H_2O_2$)-treated MG-63 cells. Expression levels of IER3, Nrf2, and heme oxygenase-1 (HO-1) were analyzed using western blot analysis. Results: Our results showed that ursolic acid up-regulated the proliferation of osteoblasts without any cytotoxic effects, and promoted ALP activity and mineralization. $H_2O_2$-induced ROS generation was found to be significantly inhibited on treatment with ursolic acid. Furthermore, in $H_2O_2$-treated cells, the expression of the early response genes: IER3, Nrf2, and Nrf2-related phase II enzyme (HO-1) was enhanced in the presence of ursolic acid. Conclusion: The key findings of the present study elucidate the protective effects of ursolic acid against oxidative stress conditions in osteoblasts via the IER3/Nrf2 pathway. Thus, ursolic acid may be developed as a preventative and therapeutic agent for mineral homeostasis and inflammatory diseases caused due to oxidative injury.