• 대한의생명과학회지
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• 제28권3호
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• pp.192-194
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• 2022

The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

• 대한치과교정학회지
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• 제46권4호
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• pp.228-241
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• 2016

Objective: Root mobility due to reciprocating movement of the tooth (jiggling) may exacerbate orthodontic root resorption (ORR). "Jiggling" describes mesiodistal or buccolingual movement of the roots of the teeth during orthodontic treatment. In the present study, buccolingual movement is described as "jiggling." We aimed to investigate the relationship between ORR and jiggling and to test for positive cell expression in odontoclasts in resorbed roots during experimental tooth movement (jiggling) in vivo. Methods: Male Wistar rats were divided into control, heavy force (HF), optimal force (OF), and jiggling force (JF) groups. The expression levels of cathepsin K, matrix metalloproteinase (MMP)-9 protein, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant 1 (CINC-1; an IL-8-related protein in rodents), receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL), and osteoprotegerin protein in the dental root were determined using immunohistochemistry. Results: On day 21, a greater number of root resorption lacunae, which contained multinucleated odontoclasts, were observed in the palatal roots of rats in the JF group than in rats from other groups. Furthermore, there was a significant increase in the numbers of cathepsin K-positive and MMP-9-positive odontoclasts in the JF group on day 21. Immunoreactivities for IL-6, CINC-1, and RANKL were stronger in resorbed roots exposed to jiggling than in the other groups on day 21. Negative reactivity was observed in the controls. Conclusions: These results suggest that jiggling may induce ORR via inflammatory cytokine production during orthodontic tooth movement, and that jiggling may be a risk factor for ORR.

• Journal of Acupuncture Research
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• 제32권3호
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• pp.15-25
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• 2015

Objectives : The purpose of this study is to investigate the effects of Pyrrosiae Herba herbal-acupuncture(PH-HA) at $KI_{10}$(Umgok) on nephritis induced by lipopolysaccharide(LPS) in rats. Methods : Rats were assigned to four groups: normal, LPS, saline and PH-HA. Rats in the saline and PH-HA groups were treated with saline injection and PH-HA respectively at $KI_{10}$, three times over the period of one week. All animals, except those in the normal group, were injected intra-peritoneally with LPS to induce nephritis. WBC, in blood, tumor necrosis factor alpha(TNF-${\alpha}$), cytokine-induced neutrophil chemoattractant 1(CINC-1), blood urea nitrogen(BUN), creatinine in serum, urinal volume, total protein creatinine in urine, and renal myeloperoxidase (MPO) were analyzed. Results : 1. PH-HA group showed significantly reduced levels of serum BUN, serum creatinine, TNF-${\alpha}$, and CINC-1 compared to the LPS group. Furthermore, a significant increase in urine output and more significant decreases in total protein in urine and MPO in renal tissue were observed in the PH-HA group when compared to the LPS group. 2. The PH-HA group showed significantly reduced levels of serum creatinine and renal MPO, and a more significant increase in urine output compared to the saline group. Conclusions : According to these results, it is postulated that PH-HA at $KI_{10}$ has anti-inflammatory and renal-protective effects on LPS-induced nephritis in rats, and both acupoint $KI_{10}$ and the herb Pyrrosiae Herba made contributions to these effects. Further studies on the interaction between acupoint $KI_{10}$ and the herb Pyrrosiae Herba may be needed.

• 대한한의학회지
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• 제36권3호
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• pp.73-83
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• 2015

Objectives: The purpose of this study was to evaluate the effects of Polyporus Herbal-acupuncture(PO-HA) at KI10 (Umgok) on nephritis induced by lipopolysaccharide(LPS) in rats. Methods: Rats were allocated into normal, control, and 2 experimental groups. The rats in the control group were intra-peritoneally injected with LPS for nephritis induction. The rats in the groups of experiment 1 and experiment 2 were treated with Saline injection, and PO-HA, respectively at KI10 three times for a week and then intra-peritoneally injected with LPS. To evaluate the effects of PO-HA at KI10, WBC count in blood, creatine, tumor necrosis factor-alpha (TNF-${\alpha}$), cytokine-induced neutrophil chemoattractant 1(CINC-1) in serum, urinary volume, creatinine, total protein in urine, myeloperoxidase(MPO) in kidney were measured. Results: PO-HA at KI10 significantly suppressed the increase of WBC in blood, TNF-${\alpha}$, CINC-1 in serum, MPO in kidney of LPS-stimulated rats. PO-HA at KI10 significantly suppressed the increase creatinine, total protein in urine of LPS-stimulated rats. Conclusions: According to these results, it is postulated that PO-HA at KI10 has an anti-inflammatory and renal-protective effects on LPS-induced nephritis in rats. Therefore, it is suggested that PO-HA at KI10 may be an useful therapeutics for nephritis in clinical field after further researches.

• 한국자원식물학회지
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• 제28권3호
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• pp.333-340
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• 2015

This study measured the plasma and liver concentrations of cytokines, the distribution of blood lymphocyte subpopulations (CD4 and CD8), plasma levels of nitrite (NO₃^–) and nitrate (NO₂^–), intercellular adhesion molecule 1 (ICAM-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), prostaglandin E2 (PGE2), and peritoneal lavage fluid (PLF) levels of monocyte chemotactic protein 1 (MCP-1) and CINC-1 in order to examine the anti-inflammatory activity of the cinnamon extract in lipopolysaccharide (LPS)-exposed rats. The plasma concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) were lower in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection. Furthermore, the liver concentrations of IL-1β, IL-6, and TNF-α were lower in the cinnamon extract groups than in the control group at 5 h after LPS injection. Plasma IL-10 concentrations were higher in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection, and liver concentrations of IL-10 did not differ significantly among all treatment groups at 5 h after LPS injection. The distribution of CD4 tended to increase, and that of CD8 tended to decrease in the cinnamon extract groups. The CD4/CD8 ratio was increased in the cinnamon extract groups. The plasma concentrations of NO₃^–/NO₂^–, ICAM-1, CINC-1, and PGE2 and the PLF concentrations of MCP-1 and CINC-1 exhibited a tendency to decrease in the cinnamon extract groups. These results indicate that cinnamon extract can exert functional anti-inflammatory effects.

• Journal of Ginseng Research
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• 제38권1호
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• pp.8-15
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• 2014

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-${\kappa}B$. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-$1{\beta}$, and iNOS; protein level of phospho-$I{\kappa}B{\alpha}$(which reflects the activation of NF-${\kappa}B$); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-$1{\beta}$, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of $I{\kappa}B{\alpha}$ and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of poly-morphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pyloriinduced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-$1{\beta}$, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

• 대한한의학회지
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• 제34권1호
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.

• Tuberculosis and Respiratory Diseases
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• 제43권6호
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• pp.945-953
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• 1996

연구배경: 진폐증을 비롯한 급만성 염증성 폐질환의 공통적인 병태생리는 활성화된 대식세포에서 분비되는 싸이토카인에 의해 염증세포 특히 독성 산화물질이나 단백분해효소 등을 분비하는 호중구의 침윤이 중요한 역할을 하며 염증이 지속되는 경우 비가역적인 섬유화를 가져오게 된다. 최근 강력한 호중구 화학주성인자로 밝혀진 IL-8은 TNF ${\alpha}$나 IL-1 에 의해 단핵세포나 대식세포, 섬유모세포등에서 분비되며 단백분해효소나 열 등에 안정하여 긴 반감기를 갖고 있어 다른 화학주성인자에 비해 지속적인 염증반응을 일으킨다. 실험 진폐증에서 유리규산에 폭로된 대식세포에서 TNF ${\alpha}$ 와 IL-1 이 증가함이 밝혀졌고, 유리규산과 같이 배양한 단핵세포에서 호중구 화학주성이 증가하며 lL-8 항체에 의해 호중구 화학주성이 억제됨이 보고된 바 있어 저자들은 IL-8 이 진폐증의 병태생리에서도 중요한 역할을 할 것으로 가정하게 되었다. 이에 진폐증 환자에서 IL-8의 분비가 증가하였는지 여부와 진폐증의 진행정도에 따른 IL-8 농도의 상관관계를 알아보고 진폐증의 조기진단에 IL-8을 생화학적 지표로 이용하고자 본 연구를 시도하였다. 방법: 분진 폭로력이 없는 아파트 경비원 16명을 대조군으로 하였고, 환자군은 흉부 X 선상 ILO 분류에 따라 의사진폐증군 16명, 소음영 진폐증군 16명, 대음영 진폐중군 16명을 대상으로 혈액 3$m{\ell}$를 채취하여 혈청을 얻은 다음 sandwich enzyme immnoassay technique 을 사용하여 IL-8을 정량분석하였다. 결과: 1. 대조군에 비하여 소음영 진폐증군과 대음영 진폐증군에서 연령이 높게 나타났으나 흡연력에는 차이가 없었으며 진폐증군사이에 분진 폭로력에도 유의한 차이는 없었다. 2. IL-8의 농도는 대조군에서 $17.85{\pm}33.85pg/m{\ell}$였던 것에 비하여 의사진폐증군에서 $70.50{\pm}53.63 pg/m{\ell}$ 소음영 진폐증군에서 $107.50{\pm}45.88pg/m{\ell}$ 대음영 진폐증군에서 $132.50{\pm}73.47pg/m{\ell}$로 대조군에 비하여 유의하게 증가하였다(p<0.001). 3. 진폐증군에서 진폐증이 진행할수록 IL-8 은 증가하는 경향을 보였고, 분산분석에서 다중비교를 하였을 때 의사진폐증군과 대음영 진폐증군사이에 통계적으로 유의한 차이가 있었다(p<0.05). 4. 진폐증 병형과 IL-8 농도사이에 상관계수는 0.4199(p<0.05)로 미약하지만 통계적으로 유의한 상관관계를 보여주었다. 결론: 진폐증의 조기진단을 위한 생화학적 지표로 IL-8 의 유용성이 클 것으로 기대되며 향후 진폐증에서의 IL-8항체의 호중구억제와 폐손상에 대한 방어 효과에 관한 연구가 이루어져야 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제63권6호
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• pp.497-506
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• 2007

연구배경: 급성호흡곤란증후군의 병인론에 관여하는 PAF의 역할이 다양하고 중요하므로 본 연구에서는 PAF의 또 다른 작용의 가능성, 즉 $cPLA_2$의 활성화(retrograde activation of $cPLA_2$ by PAF)의 가능성을 검사하고자 하였다. 즉, $cPLA_2$의 활성화에 따른 염증성 지질분자의 생성이 산소기의 생성과정을 증폭시키고 이 때 생성된 PAF가 역으로 $cPLA_2$를 활성화시키는지를 확인하기 위하여 본 연구는 고안되었다. 방 법: 흰쥐에서 급성폐손상을 유도하기 위하여 $5{\mu}g$의 PAF를 0.5 ml의 0.25% bovine serum albumin 용액과 혼합한 뒤 기도 내로 직접 분무하거나 0.5 ml의 4.5 mM의 과산화수소를 기도 내로 분무하였다. 대조군의 경우는 0.5 ml의 생리적 식염수를 기도 내로 분무하였다. 5 시간 후에 단백누출지수 측정, 폐장의 MPO 활성도 측정, 폐포 세척액 내의 호중구 산정, CINC 측정, NBT 및 cytochrome-c 환원검사를 시행하였다. 또한 폐장 및 호중구에 서의 $cPLA_2$ 활성도의 측정 및 광학현미경과 전자현미경을 이용하여 형태학적 관찰을 시행하였다. 결 과: PAF투여 후 단백누출지수, MPO, BAL내의 호중 구의 수 및 CINC의 농도가 대조군에 비하여 유의하게 증가하였다. NBT및 cytochrome-c환원검사의 결과 PAF는 호중구의 respiratory burst를 현저히 증가시키고, 분리된 사람의 호중구에서도 산소기의 생성을 현저히 증가시켰 다. 동시에 PAF는 분리된 호중구 및 폐장의 $cPLA_2$의 활성도도 증가 시켰다. 폐장 내로 투여한 과산화수소는 폐장의 $cPLA_2$활성도를 대조군에 비하여 현저히 증가시켰다. 결 론: $cPLA_2$의 활성화에 따라 생성된 PAF는 호중구의 산소기 생성을 증가시켜 폐장 내의 산화성스트레스를 유발하고 동시에 이때 생성된 산화기는 $cPLA_2$를 활성화시키며 PAF 또한 $cPLA_2$의 활성도를 증가시켜 PAF가 급성호흡 곤란증후군의 병인론에 관여하는 것으로 생각된다.