• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.48-54
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• 2005

Purpose : The pathologic mechanisms of central nervous system(CNS) injuries in human meningitis are not yet completely understood. Recent studies indicate that the host inflammatory responses are as important in brain damage as the infecting organisms and toxins. There have been some reports on the relationship of nitric oxide(NO), macrophage inflammatory protein-$1{\alpha}$(MIP-$1{\alpha}$), and lactoferrin in bacterial meningitis, but few reports in aseptic meningitis. Thus, we investigated the concentrations of NO, MIP-$1{\alpha}$ and lactoferrin in cerebrospinal fluid(CSF) and serum of patients with aseptic meningitis and control subjects and evaluated their relationship with other parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with aseptic meningitis and 15 control subjects. After centrifugation, supernatants were stored at $-70^{\circ}C$ and we assayed the concentrations of NO, MIP-$1{\alpha}$ and lactoferrin with the ELISA method. There were no patients with neurologic sequelae after being recovered from aseptic meningitis. Results : Concentrations of CSF and serum NO, MIP-$1{\alpha}$ were not increased in aseptic meningitis subjects compared to control subjects. Concentration of CSF lactoferrin was significantly elevated in patients with aseptic meningitis and concentration of serum lactoferrin was significantly decreased in patients with aseptic meningitis compared with those in control subjects(P<0.05). CSF lactoferrin level was positively correlated with CSF WBC counts($r_s=0.449$, P=0.007), especially with neutrophil counts($r_s=0.574$, P<0.001) and CSF protein level($r_s=0.508$, P=0.002). Conclusion : Lactoferrin plays an important role in aseptic meningitis and may be released from neutrophils recruited from blood to the CSF through breakdown of blood-brain barrier. NO and MIP-$1{\alpha}$ may not be important factors in the pathogenesis of aseptic meningitis without neurologic sequelae.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.107-120
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• 1993

Particulate or soluble stimuli appear to stimulate phagocytic cell's response by the change of $Ca^{2+}$ mobilization and by the activation of protein kinase C. In contrast, it is reported that activation of protein kinase C could attenuate agonist-stimulated elevation of $Ca^{2+}i$ in neutrophils. PAF elicited an increase of $Ca^{2+}i$ in peritoneal macrophages in a dose dependent fashion and $Ca^{2+}$ extrusion was accompanied. PAF-induced elevation of $Ca^{2+}i$ was not affected by TMB-8, verapamil and TTX. TEA stimulated PAF-induced mobilization of $Ca^{2+}i$ and delayed lowering of $Ca^{2+}i$. Five mM EGTA almost completely inhibited PAF-induced mobilization of $Ca^{2+}i$. After the addition of PAF, membrane permeability was markedly increased up to 5 min and then slowly increased. PAF-induced LDH release was slightly decreased by EGTA plus TMB-8. PAF-stimulated superoxide generation was inhibited by EGTA, TMB-8 and verapamil but not affected by TTX and TEA. PAF-induced elevation of $Ca^{2+}i$, increased membrane permeability and superoxide generation were inhibited by IQSP, chlorpromazine and propranolol. PAF-induced LDH release was significantly inhibited by chlorpromazine and minimally decreased by propranolol. After the pretreatment with PMA, the stimulatory effect of PAF on the elevation of $Ca^{2+}i$ and LDH release in macrophages was significantly decreased. These results suggest that PAF may exert the stimulatory action on peritoneal macrophages of mouse by the elevation of $Ca^{2+}i$ and by the activation of protein kinase C. Preactivation of protein kinase C appears to attenuate the stimulatory action of PAF on macrophage response.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.3
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• pp.309-316
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• 2008

This study was carried out to examine the effects of vitamin E on chronic gastric ulcer induced by alcohol treatment in rats. Chronic gastric ulcer model was established by oral administration of 70% ethanol at one time and supply of 15% ethanol for additional 7 days. Male Sprague-Dawley rats, approximately 200 g, were fasted for 24 hours and orally gavaged with 1 mL of 70% ethanol for the induction of acute ulcer. A supply of 15% ethanol dissolved in distilled water for 7 days were followed to maintain chronic gastric ulcer. Acute ulcer group was sacrificed at 3 hours after oral administration of 1 mL of 70% ethanol. Chronic groups were divided into three groups according to vitamin E levels; low-vitamin E (LVE, 0 mg/mL oil/day), normalvitamin E (NVE, 1 mg/mL oil/day) and high-vitamin E (HVE, 10 mg/mL oil/day). These groups were fed vitamin E free diets which were made of vitamin E free vitamin mix followed AIN-93M pattern for 7 days. Histological findings of congestion, hemorrhage and necrosis in gastric tissue were shown severely in acute ulcer group and LVE group of chronic ulcer groups. The concentration of gastrin in serum was significantly higher in LVE group. The content of histamine in stomach was lower in acute ulcer group but there was no significant difference among the chronic groups regardless of vitamin E levels. Content of malondialdehyde (MDA) in gastric tissue was higher in HVE group and activities of antioxidant enzyme, glutathione peroxidase (GPx) and catalase, were lower in HVE group. Myeloperoxidase (MPO) activities as a marker of neutrophils infiltration was significantly higher in LVE group. These results suggested that vitamin E supplementation has positive effects on healing of alcohol-induced chronic gastric ulcer through alleviation of gastric tissue injuries and reduction of the MPO activity in gastric tissue and gastrin in serum.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.