Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells

Lee, Young-Sun,Yi, Hyon-Seung,Suh, Yang-Gun,Byun, Jin-Seok,Eun, Hyuk Soo,Kim, So Yeon,Seo, Wonhyo,Jeong, Jong-Min,Choi, Won-Mook,Kim, Myung-Ho,Kim, Ji Hoon,Park, Keun-Gyu,Jeong, Won-Il Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.11

Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

고온 환경에서의 운동 시 서로 다른 수분 보충이 엘리트 운동선수들의 염증성 사이토카인 반응 및 면역 기능에 미치는 영향

백일영 ( Il Young Paik ),윤두상 ( Doo Sang Yun ),서상훈 ( Sang Hoon Suh ),노희태 ( Hee Tae Roh ) 한국스포츠정책과학원(구 한국스포츠개발원) 2011 체육과학연구 Vol.22 No.3

이 연구의 목적은 고온 환경에서의 운동 시 단순 수분 및 스포츠 음료를 통한 수분 보충이 엘리트 운동선수들의 호르몬 변화, 염증성 사이토카인 반응 및 면역 기능에 미치는 영향을 규명하는데 있다. 연구의 대상은 엘리트 운동선수 10명으로 하였으며, 4가지 실험 처치 조건에서 75%HRR 운동 강도로 60분간 트레드밀 달리기를 실시하였다: 1) 적정 환경에서 운동 처치 조건(TE), 2) 고온 환경에서 운동 처치 조건(HE), 3) 고온환경에서 운동 시 물 섭취 처치 조건(HW), 4) 고온 환경에서 운동 시 스포츠음료 섭취 처치 조건(HS). 기후조건은 인공기후실을 이용하여 적정 환경은 온도 18℃, 상대습도 50%로 설정하였으며, 고온 환경은 온도 32℃, 상대습도 50%로 설정하였다. 수분 보충은 물 또는 스포츠음료를 이용하여 고온 환경에서 운동 처치 조건(HE)의 운동 전, 후 체중 차와 동일한 양을 구강 투여하였다. 채혈은 안정 시, 운동 직후, 회복 60분 시점에서 실시하였다. 연구결과, 운동 직후 시점에서 epinephrine은 HE 처치가 다른 세 처치(TE, HW, HS)보다 유의하게 높았으며(p<.05), norepinephrine은 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). IL-6는 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). TNF-α는 TE 처치를 제외한 세 처치(HE, HW, HS)에서 운동 직후 유의하게 증가하였다(p<.05). T-cell은 TE 처치를 제외한 세 처치(HE, HW, HS)에서 운동 직후 유의하게 증가하였으며(p<.05), HE 처치가 TE 처치보다 유의하게 높았다(p<.05). NK-cell은 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). Neutrophil은 HE 처치의 경우 운동 직후 시점에서 유의하게 증가하였다(p<.05). Lymphocyte는 TE와 HE 처치에서 운동 직후 유의하게 증가하였다(p<.05). Monocyte는 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). 이상의 결과를 종합하면, 고온 환경에서의 운동은 적정 환경에서의 운동 시보다 카테콜아민과 염증성 사이토카인의 분비를 증가시켜 면역기능에 부정적인 영향을 미칠 수 있는 것으로 나타났다. 반면에 고온 환경에서의 운동 시 수분 보충은 탈수와 열적 스트레스를 경감시켜 면역기능의 부정적 영향을 완화시킬 수 있음을 시사한다. The purpose of the current research was to investigate the effects of body fluid replacement by water or sport drinks on the hormonal, inflammatory cytokine and immune responses during exercise in high ambient temperature. The subjects of the current research were 10 elite athletes. The subjects were asked to perform treadmill running at 75%HRR for 60 minutes in four different conditions, controlled by the environmental chamber: 1) thermoneutral environment (TE), 2) high ambient temperature environment (HE), 3) high ambient temperature environment and body fluid replacement by water (HW), and 4) high ambient temperature environment and body fluid replacement by sport drink(HS). Ambient temperature and relative humidity were set at 18℃ and 50%, respectively, for the theromoneutral environment, and 32℃ and 50% for the high ambient temperature environment. The amount of fluid replaced during two different fluid replacing conditions (HW and HS) were equivalent to the difference in body weight between pre and post completion of the running in HE. The defined amounts of the fluids were administered orally with separations during the exercise trials. Blood samples were taken at rest, at immediately after exercise, and at 60-minute of recovery. For catecholamine responses, the level of epinephrine immediately after exercise appeared to be significantly higher in HE compared to the other treatment conditions (p<.05), while the level of norepinephrine appeared to be significantly higher in HE compared to TE (p<.05). For cytokine responses, the level of IL-6 immediately after exercise appeared to be significantly higher in HE compared to TE (p<.05) while the levels of TNF-α were shown to significantly increase at immediately after exercise in all treatment conditions except TE (p<.05). For immune responses, the levels of T-cell were shown to significantly increase at immediately after exercise in all treatment conditions except TE (p<.05), and the level appeared to be significantly higher in HE compared to TE (p<.05); the level of NK-cell appeared to be higher at immediately after exercise in HE compare to TE (p<.05); the level of neutrophil was shown to significantly increase at immediately after exercise in HE (p<.05); the levels of lymphocyte were shown to significantly increase in TE and HE at immediately after exercise (p<.05); and the level of monocyte appeared to be significantly higher in HE compared to TE at immediately after exercise (p<.05). On the base of the results of the current study, it is suggested that exercise in high ambient temperature can induce increase responses of catecholamines and cytokines which may negatively influence on immune functions. Body fluid replacements during exercise in high ambient temperature, however, can attenuate the negative consequences of thermal stress on immune functions by preventing dehydration and reducing thermal stress.

Paradoxical psoriasis induced by biologic therapies

( Hyun Yi Suh ),( Hong Lim Kim ),( Kyung Ho Kim ),( Jae Wook Jeon ),( Ji Young Ahn ),( Mi Youn Park ),( Jai Il Youn ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Biologic therapies currently approved for the treatment of moderate-to-severe plaque psoriasis work well. Administrations of those are beneficial in a variety of chronic inflammatory conditions. Recent reports have illustrated the paradoxical development of psoriasis after biologic therapies. A 30-year-old man presented widespread scaly erythematous patches on the whole body involvement after treatment with the third dose of infliximab. He was diagnosed with palmoplantar psoriasis 6 years ago. The patients had been treated either neotigason or cyclosporine with eximer phototherapy for 2 years 6 months before visiting our psoriasis clinic. He was started on the injections of infliximab, but there was no improvement after the first dose. After receiving third dose of infliximab, the patient had experienced worsening of his plaque psoriasis on the whole. We changed other biologics, ustekinumab, anti-IL-12/23 p40 monoclonal antibody. He was treated with ustekinumab. Although receiving the second dose of ustekinumab, the skin lesions were not improved and worsening of appearing pustules on the palm and sole. We treated with cyclosporin and with calcipotriol agent (Daivonex® cream) for his skin lesion. Herein, we report this impressive case of induced paradoxical psoriasis after treating on TNF-a inhibitor and IL-12/23 inhibitor.

흰쥐의 좌골신경 절단 후 요추척수에서 소교세포의 증식과 소멸에 따른 Cytokine의 발현

김상표,서성일,조영록,조승제,김승필,박종욱,곽정식,박종욱 대한병리학회 1998 Journal of Pathology and Translational Medicine Vol.32 No.2

Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro

Oh, Bo Ram,Suh, Dong-hyeon,Bae, Daekwon,Ha, Nina,Choi, Young Il,Yoo, Hyun Jung,Park, Jin Kyun,Lee, Eun Young,Lee, Eun Bong,Song, Yeong Wook BioMed Central 2017 Arthritis research & therapy Vol.19 No.-

<P><B>Background</B></P><P>Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA).</P><P><B>Methods</B></P><P>CIA was induced by bovine type II collagen (CII) in DBA/1 J mice. Mice were treated with HDAC inhibitor for 18 days. Arthritis score was assessed and histological analysis was performed by hematoxylin and eosin (H&E) stain. Cytotoxic T-lymphocyte associated protein (CTLA)-4 expression in induced Treg cells was analyzed and suppression assay was analyzed using Treg cells and effector T (Teff) cells isolated from naive C57BL/6 mice by flow cytometry. Cytokines were analyzed in peripheral blood mononuclear cells (PBMC) of five patients with RA by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Tumor necrosis factor (TNF) was analyzed using PMA- activated THP-1 cells by ELISA. Suppression assay was analyzed using Treg cells and Teff cells isolated from RA patients by flow cytometry.</P><P><B>Results</B></P><P>In the CIA model, CKD-L and Tubastatin A significantly decreased the arthritis score. CKD-L increased CTLA-4 expression in Foxp3<SUP>+</SUP> T cells and inhibited the proliferation of Teff cells in the suppression assay. In RA PBMC, CKD-L significantly inhibited TNF and interleukin (IL)-1β, and increased IL-10. CKD-L and Tubastatin A inhibited TNF secretion from PMA-activated THP-1 cells. CKD-L and ITF 2357 inhibited the proliferation of Teff cells in RA patients in the suppression assay. Tubastatin A had no effect on inhibition of proliferation.</P><P><B>Conclusion</B></P><P>CKD-L decreased the arthritis score in CIA, reduced the expression of TNF and IL-1β, and increased the expression of IL-10 in PBMC from RA patients. CKD-L increased CTLA-4 expression and the suppressive function of Treg cells. These results suggest that CKD-L may have a beneficial effect in the treatment of RA.</P>

고교 축구선수의 경기 후 회복방법의 차이가 혈중 염증, 근 손상 및 피로 지표에 미치는 영향

백승훈(Seung Hoon Paik),백일영(Il Young Paik),서상훈(Sang Hoon Suh),조수연(Su Youn Cho),노희태(Hee Tae Roh) 한국사회체육학회 2014 한국사회체육학회지 Vol.0 No.56

The purpose of the current study was to investigate the effects of different recovery treatments on serum inflammation, muscle damage and fatigue variables after a game of soccer players in high school. The subjects of current study were 10 soccer players in high school without any medical complications. All subjects received both recovery treatments (contrast bath and massage) for once and a control application; therefore, all underwent 3 experimental conditions. Blood sampling taken at rest, at immediately after the match, and at 60 minutes recovery. From the three blood samples, the parameters of inflammation and fatigue were analyzed. Additional blood sampling was taken at 24 hours recovery for the analysis of the long term effect of the applications on the parameters of muscle damage. The concentration of interleukin-6(IL-6), creatine kinase(CK), lactate dehydrogenase (LDH), and lactate were shown to significantly increase at immediately after the match in all experimental conditions(p<.05). For inflammation responses the concentration of IL-6 60min recovery appeared to be significantly lower in contrast bath and massage treatments compared to control treatment(p<.05). Also, for muscle damages the concentration of CK 24h recovery appeared to be significantly lower in massage treatment compared to contrast bath and control treatments(p<.05). On the base of the results of the current study, it is suggested that soccer match can induce increased concentrations of IL-6, CK, LDH and lactate which may influence on inflammation, muscle damage and fatigue. However, contrast bath and massage were beneficial for recovery from muscle damage.

금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향

이동언,이재령,김영우,권영규,변성희,신상우,서성일,권택규,변준석,김상찬,Lee, Dong-Eun,Lee, Jae-Ryung,Kim, Young-Woo,Kwon, Young-Kyu,Byun, Sung-Hui,Shin, Sang-Woo,Suh, Seong-Il,Kwon, Taeg-Kyu,Byun, Joon-Seok,Kim, Sang-Chan 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.2

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

Inhibitory Effect of Farfarae Flos Water Extract on COX-2, iNOS Expression and Nitric Oxide Production in lipopolysaccharide - activated RAW 264.7 cells

Yoon Tae Gyoung,Byun Boo Hyeong,Kwon Teag Kyu,Suh Seong Il,Byun Sung Hui,Kwon Young Kyu,Kim Sang Chan The Physiological Society of Korean Medicine and T 2004 동의생리병리학회지 Vol.18 No.3

Farfrae Flos has been clinically used for the treatment of asthma in traditional oriental medicine. There is lack of studies regarding the effects of Farfrae Flos on the immunological activities. The present study was conducted to evaluate the effect of Farfrae Flos on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, Farfrae Flos water extract inhibited nitric oxide production in a dose-dependent manner and abrogated inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Farfrae Flos water extract did not affect on cell viability. To investigate the mechanism by which Farfrae Flos water extract inhibits iNOS and COX-2 gene expression, we examined the on the phospholylation of inhibitor κBα and production of TNF-α, IL-1β and IL-6. Results provided evidence that Farfrae Flos inhibited the production of interleukin-1β (IL-1β) and the activation of phospholylation of inhibitor κBα in Raw 264.7 cells activated with LPS. These findings suggest that Farfrae Flos can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

桑黃 물추출물이 LPS로 유도된 Raw 264.7 cell에서의 TNF-α, IL-1β, IL-6 및 Nitric Oxide production에 미치는 영향

김상찬(Sang Chan Kim),정연숙(Youn Suk Jung),이재령(Jae Ryung Lee),김영우(Young Woo Kim),변부형(Boo Hyeong Byun),권택규(Teag Kyu Kwon),서성일(Seong Il Suh),변성희(Sung Hui Byun),권영규(Young Kyu Kwon) 한의병리학회 2004 동의생리병리학회지 Vol.18 No.3

X-線粉末廻折法에 의한 Cadmiun Sufide 試料의 定量定性分析

徐日煥,金永銓,鄭濟永 충남대학교 자연과학연구소 1983 忠南科學硏究誌 Vol.10 No.1

The 32 X-ray diffraction intensity peaks for the cadmium sulfide powder (99.999% purity),which is an industrially important semiconductor, were obtained rotating 2θh㎘ Bragg angle of X-ray diffractometer with Cu Kα radiation from 20 to 120 degrees by θ-2θ scan technique. Each reflecting plane identified by means of the graphical and analytical methods indicated that there are two different kinds of phases : hexagonal close-packed structure with a=4.13Å, c=6.75Å and face-centered cubic structure with a=5.82Å. In order to account for the result of two molecules per unit hexagonal cell and four molecules per unit cubic cell, they should have the wurtzite form and zinc blende form respectively. The quantitative analysis by the direct comparison method has shown that this sample contains approximately 86.3 percent wurtzite form and the rest 13.7 percent zinc blende form of CdS. The correct result has been proved by the good agreement between the experimental and theoretical integrated intensities.