• International Journal of Oral Biology
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• v.41 no.4
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• pp.217-223
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• 2016

Porphyromonas gingivalis, a foremost periodontal pathogen, has been known to cause periodontal diseases. Epidemiologic evidences have indicated the involvement of P. gingivalis in the development of cardiovascular diseases. In this study, we show that the P. gingivalis lipopolysaccharide increases the mRNA expression and protein secretion of interleukin-6 in vascular smooth muscle cells. We demonstrate that P. gingivalis LPS activates the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and Akt, which mediate the IL-6 expression in vascular smooth muscle cells. Also, P. gingivalis LPS stimulates the vascular smooth muscle cell migration, which is a critical step for the progression of atherosclerosis. Moreover, neutralization of the IL-6 function inhibits the migration of vascular smooth muscle cells induced by P. gingivalis LPS. Taken together, these results indicate that P. gingivalis LPS promotes the expression of IL-6, which in turn increases the migration of vascular smooth muscle cells.

• KSBB Journal
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• v.28 no.1
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• pp.7-12
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• 2013

Thromboxane $A_2$ ($TXA_2$) is one of major proinflammatory mediators, plays an important role in the development of vascular inflammatory diseases. $TXA_2$ acting through the thromboxane receptor regulates multiple pathways and genes in a variety of cells. In this study, we report that the activation of thromboxane receptor with U46619 increases the interleukin-8 (IL-8) mRNA in vascular endothelial cells. We also demonstrated that U46619 produces the activations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK), which is required for endothelial IL-8 production. And U46619 enhanced mRNA stability of IL-8 transcripts in endothelial cells. Moreover, inhibition of ERK1/2 or p38MAPK reduced monocyte adhesion to aortic endothelium stimulated by U46619. Therefore, these results suggest that activation of thromboxane receptor promotes the expression of IL-8 via ERK1/2 and p38MAPK activation in endothelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.253-258
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• 2008

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.23-27
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• 2005

The present study was performed to investigate the effects of intra-articular injection of interleukin-1${\beta}$ (IL-1${\beta}$) on the formalin-induced temporomandibular joint (TMJ) pain. Under anesthesia, a 30-gauge needle was introduced into the right TMJ region for injection of formalin. Microinjection of 50 ${\mu}l$ of 5% formalin significantly produced noxious scratching behavioral response, and the scratching behavior lasted for 40 min. Although the responses produced by formalin injection were divided into two phases, the response of 1st phase did not significantly differ from the scratching behavior response in the saline-treated group. We examined the effects of intra-articular injection of IL-1${\beta}$ on the number of noxious behavioral responses produced by 50${\mu}l$ of 5% formalin injection. Intra-articular injection of 100 pg and 1 ng of IL-1${\beta}$ significantly increased the number of behavioral responses of the 2nd phase, while 10 pg of IL-1${\beta}$ did not change the formalin-induced behavioral responses. To investigate whether IL-1 receptor was involved in the intra-articular administration of IL-1${\beta}$-induced hyperalgesic response, IL-1 receptor antagonist (IL- ra, 50 ng) was administrated together with IL-1${\beta}$ injection. IL-1${\beta}$ receptor antagonist blocked IL-1${\beta}$- induced hyperalgesic response in the TMJ formalin test. These results suggest that intra-articular injection of IL-1${\beta}$ facilitated the transmission of nociceptive information in the TMJ area.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.83-88
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• 2004

The purpose of this study was to provide a basis for studying the molecular mechanism of pharmacological action of chlorhexidine digluconate. Large unilamellar vesicles (OPGTL) were prepared with total lipids extracted from cultured Porphyromonas gingivalis outer membranes (OPG). The anthroyloxy probes were located at a graded series of depths inside a membrane, depending on its substitution position (n) in the aliphatic chain. Fluorescence polarization of n-(9-anthroyloxy)stearic acid was used to examine effects of chlorhexidine digluconate on differential rotational mobility, while changing the probes' substitution position (n) in the membrane phospholipids aliphatic chain. Magnitude of the rotational mobility of the intact six membrane components differed depending on the substitution position in the descending order of 16-(9-anthroyloxy)palmitic acid (16-AP), 12, 9, 6, 3 and 2-(9-anthroyloxy)stearic acid (12-AS, 9-AS, 6-AS, 3-AS and 2-AS). Chlorhexidine digluconate increased in a dose-dependent manner the rate of rotational mobility of hydrocarbon interior of the OPGTL prepared with total lipids extracted from cultured OPG, but decreased the mobility of membrane interface of the OPGTL. Disordering or ordering effects of chlorhexidine digluconate on membrane lipids may be responsible for some, but not all of its bacteriostatic and bactericidal actions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.199-203
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• 2007

Dental caries is a major worldwide oral disease problem. Streptococcus mutans (S. mutans) plays an important role in the information of dental plaque and it is being noticed as major causative bacteria of dental caries. Therefore, the development of more effective, substantial and safe preventive agents against dental caries is strongly required. In the present study, inhibitory effects of the ethanol extract of the husk of pomegranate (Punica granatum L.) on the growth, acid production, adhesion and water-insoluble glucan synthesis of Streptococcus mutans (S. mutans) were examined. The ethanol extract of pomegranate husk (250 - 4000 ${\mu}$g/ml) significantly lowered the growth of S. mutans in a dose dependent manner. The acid production of S. mutans were inhibited by the presence of ethanol extract of pomegranate husk (500 - 4000 ${\mu}$g/ml) significantly. The ethanol extract of pomegranate husk (5000 - 4000 ${\mu}$g/ml) also significantly lowered the adherence of S. mutans. In water-insoluble glucan synthesis assay, 1000 - 4000 ${\mu}$g/ml of the ethanol extract of pomegranate husk significantly inhibited the formation of water-insoluble glucan. These results suggest that pomegranate husk may inhibit the caries-inducing properties of S. mutans. Further studies are necessary to clarify the active constituents of pomegranate husk responsible for such biomolecular activities.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.13-17
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• 2006

Experimentally induced cortical disorganization exhibits many anatomical features which are characteristic of cortical malformations in children with early-onset epilepsy. We used an immunocytochemical technique and extracellular field potential recordings from the dorsal hippocampus to determine whether the excitability of the CA1 pyramidal cells was enhanced in rats with exnerimentallv induced hippocampal dysplasia. Compared with control rats, the MAM-treated rats displayed a decrease of paired pulse inhibition. When $GABA_A$ receptor antagonists were blocked with $10{\mu}M$ bicuculline the amplitude of the second population spike of the MAM-treated of rats was similar to that of the first population spike, as was in the control rats. The MAM-treated rats had fewer somatostatin and parvalbumin-immunoreactive neurons than the control rats. These results suggest that the enhanced neuronal responsiveness of the in vivo recording of the CA1 in this animal model may involve a reduction of CA1 inhibition.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.2
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• pp.91-99
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• 2019

Background: The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods: The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results: ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions: We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing.

• Restorative Dentistry and Endodontics
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• v.29 no.3
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• pp.239-248
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• 2004

The purpose of this study was to investigate the influence of NK1 receptor antagonists on the pulpal blood flow (PBF) when applied iontophoretically through the dentinal cavity of the teeth in order to understand whether iontophoretically applied NK1 receptor antagonists can control the pulpal inflammation. Eleven cats were anesthetized with alpha-chloralose and urethane, and substance P (SP) was administered to the dental pulp through the catheterized lingual artery in doses that caused PBF change without the influence of systemic blood pressure. NK1 receptor antagonists were applied iontophoretically to the prepared dentinal cavity of ipsilateral canine teeth of the drug administration, and PBF was monitored. Data were analyzed statistically with paired t-test. PBF increase after iontophoretic application of the NK1 receptor antagonists followed by the intra-arterial administration of SP was significantly less than PBF increase after iontophoretic application of the 0.9% saline followed by the intra-arterial administration of SP as a control (p < 0.05). Iontophoretic application of the NK1 receptor antagonists (0.2~3.4 mM) following the intra-arterial administration of SP resulted in less increase of PBF than the iontophoretic application of the 0.9% saline following the intra-arterial administration of SP as a control (p < 0.05). Therefore. the results of the present study provide evidences that the iontophoretic application is an effective method to deliver drugs to the dental pulp. and that iontophoretically applied NK1 receptor antagonists block SP-induced vasodilation effectively. The above results show the possibility that the iontophoretical application of NK1 receptor antagonists can control the neurogenic inflammation in the dental pulp.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.447-456
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• 2022

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.