담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

Son, Il-Hong,Park, Yong-Hoon,Yang, Hyun-Duk,Lee, Sung-Ik,Han, Sun-Jung,Lee, Jai-Kyoo,Ha, Dae-Ho,Kang, Hyung-Won,Park, Joo-Young,Lee, Sung-Soo The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.2

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

Minjung Chae,Eui-dong Son,Il-Hong Bae,조은경,Hyoung-June KIM,Ji-Yong Jung 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

Cheon, Yun-Hong,Lee, Seung-Geun,Kim, Mingyo,Kim, Hyun-Ok,Sun Suh, Young,Park, Ki-Soo,Kim, Rock Bum,Yang, Hyun-Su,Kim, Ji-Min,Son, Chang-Nam,Kyoung Park, Eun,Kim, Sang-Hyon,Lee, Sang-Il Elsevier 2018 Brain, behavior, and immunity Vol.73 No.-

<P><B>Abstract</B></P> <P>Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22–4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01–2.53]) and severity of fatigue (OR 1.26 95% CI 1.15–1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one’s capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prevalence of depression in patients with rheumatoid arthritis (RA) was analyzed. </LI> <LI> Risk factors for depression and deterioration of depressive symptoms and were analyzed. </LI> <LI> Depression was related with disease activity in RA. </LI> <LI> Depression in RA was associated with impaired ability to perform activities of daily life. </LI> <LI> Among neurotrophic factors, the level of BDNF was related with depression in RA patients. </LI> <LI> The level of pro-inflammatory cytokines were not related with depression in RA patients. </LI> </UL> </P>

우측 팔에 발생한 골격외 유잉육종 1례

김상일,송홍석,손승원 啓明大學校 醫科大學 1998 계명의대학술지 Vol.17 No.4

저자들은 53세 남자환자가 우측 팔의 무통성 종괴를 주소로 내원하여 조직검사상 골격외 유잉육종으로 판명되어 광범위절제술, 항암화학요법 및 방사선치료로 완치를 보인 1례를 경험하였기에 이에 문헌고찰과 함께 보고하는 바이다. Extraskeletal Ewing's sarcoma is a rare primary malignant soft tissue tumor that was first described by Angervall and Enzinger in 1975. These tumors tend to occur chiefly in young adults. Because of their undifferentiated histologic appearance, the differential diagnosis must exclude other small round cell neoplasm such as neuroblastoma, rhabdomyosarcoma, neuroepithelioma, and poorly differentiated malignant lymphoma. The extraskeletal Ewing's sarcoma are mainly involved the soft tissues of the trunk and lower extremity. We recently experienced a case of extraskeletal Ewing's sarcoma of the right arm in a 53 years old male. The patient underwent local wide excision and postoperative radiation of 6.480cGy and combination chemotherapy with VP-16, adriamycin, vincristine, prednisolone and cyclophosphamide. We presented a case of extraskeletal Ewing's sarcoma in the right arm with review of world literature.

Primary Empty Sella 증후군 1례

이홍준,손일진,정은경,문경래,박상기,박영봉 조선대학교 1993 The Medical Journal of Chosun University Vol.18 No.2

The pimapty sella syndrome results from and extension of the subarachnoid space into and intrasellar position with subsequent remodeling of the sella turcica and flattening of the pituitary gland. We experienced a case of primary emty sella syndrome in a 14-year-old male patient who was hospitalized because of short stature and micropenis. The endocrinologic studies revealed growth hormone and gonadotropin hormone deficiencies. The magnetic resonance imaging showed sella turica filled with CSF and flattened pituitary glad. The patient was followed-up with growth hormone therapy and the result was favorable.

콩의 개화기전후 공급과 수용부위의 무기영양성분함량 및 흡수량에 대한 질소의 효과

박재홍,송범헌,이철원,손석용,김홍식,박상일 忠北大學校 農業科學硏究所 2002 農業科學硏究 Vol.19 No.-

This study was conducted to examine the nitrogen effects on the uptaken amounts and utilization of mineral nutrients between source and sink tissues at major growth stages before and after the flowering stage with different nitrogen levels Hwangkeum cultivar(Glycine max L Mereill) was cultivated under five different mtrogen levels, 0, 2, 4, 6, 8 N kg/10a Comparing contents of total-N with different plant tissues at major growth stages before and after the flowering, total-N contents of leaves was gradually decreased from the flowering to the beginning maturity, while it of pod was continuously increased from the full seed to the beginning maturity Total-N content was higher in the treatment of 4 N Kg/10a that those of others The uptaken amount of N determined with different growth stage was rapidly increased maturity Higher proportion of uptaken N were into the leaves at the full seed stage, and they were transported from the leaves into pod at the beginning maturity stage Comparing major mineral elements of the leaves and the pod with different N leaves, in case of the leaves, the content of Fe, Mn, and Zn was decreased throughout the growth stages, whereas the content of Ca and Mg was decreased from the flowering to the full seed and then it was increased after the full seed stage In case of pod, the content of K, Fe, Mn, Zn, and Na was decreased from the flowering to the beginning maturity, while contest of Mg was increased.

콩의 개화기 전후 공급과 수용부위의 생장반응과 수량에 대한 질소의 효과

박재홍,송범헌,이철원,손석용,김홍식,박상일 忠北大學校 農業科學硏究所 2002 農業科學硏究 Vol.19 No.-

This study was conducted to examine the nitrogen effects on the growth responses, the nodulation, and the distribution of dry weight of plant tissues at major growth stages before and after the flowering stage, and to evaluate the yield components and yields with different nitrogen levels. Hwangkeum cultivar(Glycine max L mereill) was cultivated under five different nitrogen levels, 0, 2, 4, 6, 8, N Kg/10a. Stem length and branching number, which were investigated with different N levels at major growth stages, were rapidly increased for 14days for before and after the flowering stage compared to the other growth stages. They were clearly higher with treatment of 2 and 4 N kg/10a than those of other N treatments. Pod number was slightly increased from the flowering to beginning maturity. It was the highest in the treatment of 2 N Kg/10a. Comparing grain number per pod with different N levels, two grains per pod was much higher in all N treatments except for the treatment of 6 N Kg/10a. Dry weight of shoot(including leaf, stem, and pod) was rapidly increased from the flowering stage to the full seed stage and then gradually increased after the full seed stage, whereas the dry weight of root(including the nodule and root) was rapidly increased until to full pod stage and then linearly decreased from the full pod stage until the beginning maturity stage. Comparing dry weight with different N levels, the dry weight of shoot was the highest in the treatment of 4 N Kg/10a, while it of root was the highest in the treatment of 2N Kg/10a. The dry weight of nodule was the highest, 13.1 Kg/10a, at full pod stage. Comparing the dry weight of nodule with different N levels, it was increased to the application amount of 4 N Kg/10a and then clearly decreased with more application amount of N than 4 Kg/10a. The yield components which were mostly affected to the yield were pod number per plant and grain number per plant. They were 57.5 and 106.1, respectively, with treatment of 4 N Kg/10a, which showed the highest yield, about 266 Kg/10a. Comparing yield index with different N levels to the control, the yields with treatment of 2 and 4 Kg/10a were increased to 21% and 34%, respectively.

반대측 선조체에 점삼 출현이 동반된 비케톤성 고혈당성 무도증

이재규,손일홍 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

Hemichorea is usually caused by lesions in the contralateral subthalamus and/or basal ganglia. Brain MRI shows a high signal intensity on T1-weighted images and brain CT shows a hyperdense lesion in the contralateral lentiform nucleus in patients with nonketotic hyperglycemic chorea. It is not unclear that these pathophysiological mechanisms is ischemia or petechial hemorrhage. A 78 year-old woman with uncontrolled diabetic mellitus presented with sudden involuntary movement in the right limbs. Brain CT on the first HD(hospital day) revealed hyperdensity in the left lentiform nucleus and Brain MRI on the 2nd HD showed high signal intensity on Tl-weighted images in the left lentiform nucleus. After 2 month later, involuntrary movment was subsided, and the density was more decreased on follow-up brain CT. We suggest a possibility that nonketotic hyperglycemic hemichorea is associated with petechial hemorrhage in the contralateral lentiform nucleus. 편측무도증은 대부분 반대측 선조체의 문제로 발생된다. 비케톤성 고혈당 편측 무도증을 가지고 있는 환자의 뇌 단층촬영(Brain CT)에서 반대측 선조체의 고음영이 관찰되었고 뇌 자기공명영상(Brain MRI)에서는 T1 강조영상에서 고신호로 강조되었다. 하지만 고혈당과 관련된 편측 무도증의 정확한 기전은 아직도 명확하지 않으며 점상출혈이나 허혈성 변화일 것으로 추정되고 있다. 당뇨가 잘 조절되지 않는 78세 여자환자가 내원 20일전부터 발생한 우측 팔, 다리의 불수의적인 움직임을 주소로 입원하였다. 내원 초기 brain CT에서는 좌측 선조체의 고음영이 관찰되었고 Brain MRI에서는 T1 강조영상에서 고신호를 보였다. 증상 호전 보이면서 추적 관찰한 Brain MRI에서 이 병소는 T1 강조영상에서 고신호 강도가 더욱 증가하였으며, gradient echo에서는 저신호 강도가 더욱 증가하였다. 이후 증상이 더욱 호전되었고, Brian CT에서는 반대측 선조체의 고밀도 소견이 감소한 양상 관찰되어 점상 출혈 기전과 관련된 증례로 추정하여 보고하는 바이다.

점포내 VMD요소가 SPA 브랜드 정체성에 미치는 영향

김소영, 손지훈, 심효진, 신동훈, 정일호, 홍동우, 김은영 충북대학교 생활과학연구소 2013 생활과학연구논총 Vol.17 No.2

This study was to examine the effect of VMD factors on brand identity for SPA brands. As brand stimulus, four SPA brands(e.g., Basic House, Codes combine, Uniqlo, Zara) were selected by pretest. For collecting data, a self-administered questionnaire was developed based on the literatures and intercept survey was conducted. A total 508 usable responses were obtained from consumers who shopped at the selected brands' stores. For data analysis, descriptive statistics, factor analysis, and regression analysis were used. As perceived by consumers, VMD consisted of seven factors: lightening, scent, color, layout, music, window display, and item presentation. The VMD factor was significantly related to brand identity for the SPA brands. Specifically, brand awareness was predicted by color, layout and item presentation; brand association strength was predicted by color, layout, and widow display; favorable brand association was predicted by item presentation; salience of brand association was predicted by color and music; and brand image association was predicted by color, layout, music, and item presentation. Thus, this study discussed a managerial implication for SPA retailers to develop a visual merchandising strategy in the competitive marketplace.