• Journal of Korean Neurosurgical Society
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• v.48 no.1
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• pp.1-7
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• 2010

Objective : Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. Methods : Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). Results : AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-$1{\beta}$, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-$1{\beta}$, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. Conclusion : We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.291-297
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• 2015

An oral environment is constantly exposed to environmental factors and microorganisms. The periodontal ligament (PDL) fibroblasts within this environment are subject to bacterial infection and allergic reaction. However, how these condition affect PDL fibroblasts has yet to be elucidated. PDL fibroblasts were isolated from healthy donors. We examined using reverse transcription-polymerase chain reaction and measuring the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$). This study investigated the receptors activated by exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and allergens (German cockroach extract and house dust mite) as well as these pathogenic mediators-induced effects on the intracellular $Ca^{2+}$ signaling in human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory cytokines (interleukin (IL)-$1{\beta}$, IL-6, and IL-8) and bone remodeling mediators (receptor activator of NF-${\kappa}B$ ligand and osteoprotegerin) and intracellular $Ca^{2+}$-involved effect. Bacterial pathogens and allergic mediators induced increased expression of pro-inflammatory cytokines, and these results are dependent on intracellular $Ca^{2+}$. However, bacterial pathogens and allergic mediators did not lead to increased expression of bone remodeling mediators, except lipopolysaccharide-induced effect on receptor activator of NF-${\kappa}B$ ligand expression. These experiments provide evidence that a pathogens and allergens-induced increase in $[Ca^{2+}]_i$ affects the inflammatory response in human PDL fibroblasts.

• Journal of Korean Neurosurgical Society
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• v.60 no.1
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• pp.40-46
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• 2017

Objective: To assess role of some inflammatory mediators in patients with primary and recurrent lumbar disc herniation. Expression of IL-6, transforming growth factor (TGF)-1, insulin-like growth factor (IGF)-1, and Bcl-2-associated X protein (BAX) have been shown to be more intense in the primary group than the recurrent goup, but this mediators may be important aspects prognostic. Methods: 19 patients underwent primary and revision operations between June 1, 2009 and June 1, 2014, and they were included in this study. The 19 patients' intervertebral disc specimens obtained from the primary procedures and reoperations were evaluated. Expression of IL-6, TGF-1, IGF-1, and BAX were examined immunohistochemically in the 38 biopsy tissues obtained from the primary and recurrent herniated intervertebral discs during the operation. Results: For IL-6 expression in the intervertebral disc specimens, there was no difference between the groups. The immunohistochemical study showed that the intervertebral disc specimens in the primary group were stained intensely by TGF-1 compared with the recurrent group. Expression of IGF-1 in the primary group was found moderate. In contrast, in the recurrent group of patients was mild expression of IGF-1. The primary group intervertebral disc specimens were stained moderately by BAX compared with the recurrent group. Conclusion: The results of our prognostic evaluation of patients in the recurrent group who were operated due to disc herniation suggest that mediators may be important parameters.

• The Korea Journal of Herbology
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• v.22 no.4
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• pp.109-116
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• 2007

Objectives : In the present study, we investigated anti-inflammatory effects of chloroform fraction of Coptidis rhizoma (CR-C) on the production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines, tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin-1beta (IL-1${\beta}$) in LPS-stimulated BV2 microglial cells. Methods : Copriditis rhizoma was extracted with 80% methanol, and then extracted with chloroform. BV2 cells were pre-treated with CR-C, and stimulated with LPS. The cytotoxicity was determined by MTT assay. The production of NO and cytokines was measured by Griess assay and ELISA. The mRNA expression of inducible nirtic oxide synthase (iNOS) and cytokines were determined by RT-PCR. Results : CR-C significantly inhibited the production of NO. TNF-${\alpha}$ and IL-1${\beta}$ in a dose-dependent manner in LPS-stimulated BV2 cells. In addition, CR-C suppressed the mRNA expressions of iNOS and inflammatory cytokines induced by LPS stimulation. These results indicate that CR-C was involved in anti-inflammatory effects in activated microglia. Conclusion : The present study suggests that chloroform extract of Coptidis rhizoma can be useful as a potential anti-inflammatory agent for treatment of various neurodegenerative diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1598-1603
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• 2006

Activated mast cells play pivotal roles in allergic and non-allergic inflammatory responses through the release of inflammatory mediators such as histamin, cysteinyl leukotriens, pro-inflammatory cytokines as well as chemokine. We tested whether YHJST, which is clinically prescribed for the treatment of various inflammatory disease including allergic disease, modulate inflammatory reactions in activated mast cells. YHJST decreased the release of histamine and b-hexosamidase in pholbol-12-myristate 13-acetate and/or calcium ionophore A23187 stimulated HMC-1 and RBL-2H3 cells, respectively. Further, the gene expressions of tumor necrosis factor-a, IL-6 and IL-8 were significantly reduced by YHJST. YHJST suppressed powerful induction of NF-kB promoter-mediated luciferase activity. Taken together, these data suggested that YHJST showed it's anti-inflammatory effects through the down-regulation of mast cell activation.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.62-67
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• 2004

Trauma remains one of the important sources leading to systemic inflammatory response anti sub-sequent multiple organ failure. Although hepatic microvascular dysfunction occurs during trauma, the mechanism responsible remains unclear. The aim of this study was to investigate the effect of trauma on hepatic vascular stress gene expression. Femur fracture (EFx) was induced by torsion to the femur at midshaft. Liver samples were taken for RT-PCR analysis of mRNA for gtenes of interest: endothelin-1 (ET-1), its receptors $ET_A$ and $ET_B$, nitric oxide synthases (iNOS and eNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and tumor necrosis tactor-${\alpha}$ (TNF-${\alpha}$). The expression of ET-1 mRNA was significantly increased by FFx. Expression of mRNA in FFx group showed no change in $ET_A$, $ET_B$, iNOS and HO-1 and showed a slight increase of 2.2-fold and 2.7-fold for eNOS tll1d COX-2, respectively. The level of TNF-${\alpha}$ mRNA significantly increased in FFx group. In conclusion, mild trauma alone causes little change in expression of vasoactive mediators.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• Natural Product Sciences
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• v.15 no.4
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• pp.185-191
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• 2009

Intestinal epithelial cells (IEC) play an important role in the mucosal immune system. IEC-derived mediators of inflammatory cascades play a principal role in the development of colon inflammation. The aim of this study was to investigate the inhibitory effect of aqueous extracts of Schizandra chinensis fruits (SC-Ex) on the production of inflammatory mediators by the human colonic epithelial cells. HT-29 cells were stimulated with dextran sulfate sodium in the presence or absence of SC-Ex to examine the cytoprotection and production of IL-8 and reactive oxygen species (ROS). It was shown that dextran sulfate sodium (DSS) caused the reduction of cell viability and production of IL-8 and ROS in DSS-treated HT-29 cells. We observed that the treatment of SC-Ex protected significantly cell proliferation from DSS-induced damage in dose-dependent manner. SC-Ex (10 and 100 ${\mu}g$/ml) also suppressed DSS-induced production of IL-8 mRNA and protein. Moreover, DSS-induced ROS production was inhibited markedly by the treatment of 100 ${\mu}g$/ml SC-Ex. These results suggest that SC-Ex has the protective effects on DSS-induced cell damage and the release of inflammatory mediators in the intestinal epithelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.81-89
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• 2018

This study evaluated the anti-asthmatic activities of 2,6-di-tert-butyl-4-hydroxymethylphenol (DBHP) that is a potent phenolic antioxidant in edible vegetable oil. The effects of DBHP on bronchial asthma were evaluated by determining the specific airway resistance (sRaw) and tidal volume (TV) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with aerosolized ovalbumin-induced asthma. Recruitment of leukocytes and the levels of biochemical inflammatory mediators were determined in the bronchoalveolar lavage fluids (BALFs), and histopathological surveys performed in lung tissues. DBHP significantly inhibited the increased sRaw and improved the decreased TV on IAR and LAR, and also inhibited recruitment of eosinophils and neutrophils into the lung, and release of biochemical inflammatory mediators such as histamine and phospholipase $A_2$ from these infiltrated leukocytes, and improved pathological changes. However, anti-asthmatic activities of DBHP at oral doses of 12.5 to 50 mg/kg was less than those of dexamethasone (5 mg/kg, p.o.) and cromoglycate (10 mg/kg, p.o.), but more potent or similar to that of salbutamol (5 mg/kg, p.o.). These results in the present study suggest that anti-asthmatic effects of DBHP in the guinea pigs model of OVA-induced asthmatic responses principally are mediated by inhibiting the recruitments of the leukocytes and the release of biochemical inflammatory mediators from these infiltrated leukocytes.

• Korean Journal of Veterinary Research
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• v.39 no.2
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• pp.301-310
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• 1999

Anthrax caused by Bacillus anthracis is one of the most important zoonotic diseases. The bacterium produces several virulence factors. Of the factors, protective antigen (PA) of tripatite toxin has been identified as a central component in the pathogenesis of anthrax. However, precise roles of PA and other cellular components in the reaction with the target cells remain to be elucidated, especially in the initial stage of the disease. Three B anthracis antigens were prepared for investigation; PA, sonicated cellular antigens (S-Ag) and formalin-inactivaed whole cell antigens (W-Ag). PA was purified from culture supernatant of the bacterium using FPLC system with MonoQ. S-Ag and W-Ag were prepared by sonication and formalin inactivation of the cultured cells, respectively. Purity of the antigens was confirmed by SDS-PAGE and Western blot analysis. The roles of these antigens in the production of inflammatory mediators such as NO, IL-6 and $TNF{\alpha}$ from mouse peritoneal macrophages were investigated. PA alone did not induce the production of the inflammatory mediators while the other antigens, S-Ag and W-Ag, did in a dose and time dependent manner. These results suggested that in addition to major virulence factors, other cellular antigens are also involved in the initial stage of the disease by the induction of inflammatory mediators.