(2S)-2′-Methoxykurarinone from Sophora flavescens Suppresses Cutaneous T Cell-Attracting Chemokine/CCL27 Expression Induced by Interleukin-β/Tumor Necrosis Factor-α via Heme Oxygenase-1 in Human Keratinocytes

Seung-Il Jeong,Young-Eun Lee,Seon Il Jang 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.5

One of the CC chemokines, cutaneous T cell-attracting chemokine (CTACK/CCL27), is a skin-specific CC chemokine that is produced constitutively by keratinocytes and is highly up-regulated in inflammatory skin conditions such as atopic dermatitis and contact dermatitis. (2S)-2′-Methoxykurarinone (MOK) from Sophora flavescens has been demonstrated to have antioxidant effects. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. This study aimed to define whether and how MOK regulates skin specific CTACK/CCL27 chemokine production in human HaCaT keratinocytes. The level of CTACK/CCL27 and HO-1 expression was measured by reverse transcription-polymerase chain reaction, and signaling was evaluated by western blot analysis. CTACK/CCL27 production was determined by enzyme-linked immunosorbent assay. Pretreatment with MOK suppressed tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced CTACK/CCL27 production in human HaCaT keratinocytes. MOK inhibited TNF-α- and IL-1β-induced nuclear factor κB (NF-κB) activation. Interestingly, pretreatment with MOK significantly suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production through the induction of HO-1. This suppression was completely abolished by HO-1 small interfering RNA. Furthermore, carbon monoxide, but not other end products of HO-1 activity, also suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production. These results demonstrate that MOK attenuates TNF-α- and IL-1β-induced production of CTACK/CCL27 in human HaCaT keratinocytes by inhibiting NF-κB activation and induction of HO-1.

N-Acetyl-L-Cysteine에 의한 생쥐 골수유래 가지세포의 기능적 활성화 저해

정영주(Young-joo Jeong),맹형건(Hyung Gun Maeng),김민규(Min Kyu Kim),강재승(Jae Seung Kang),이왕재(Wang Jae Lee),황영일(Young-il Hwang) 대한해부학회 2008 Anatomy & Cell Biology Vol.41 No.2

N-acetyl-L-cysteine (NAC)은 thiol기를 포함하는 화합물로서, glutathione (GSH)의 전구체로 작용하여 포유류 세포 내에서 항산화제로 작용한다. 또한 항염기능이 있으며 호산구나 B세포, 가지세포 (dendritic cell, DC)와 같은 면역세포 들에 여러 가지 영향을 미치는 것으로 알려져 있다. 특히 가지세포에 작용하여 활성화를 억제하거나 가지세포에 의한 Th2 반응 유도에 관여한다고 알려져 있다. 그러나 이들 연구는 세부적인 사항에 있어서 그 결과가 서로 상치하는바가 많으며, 또한 조절T세포의 관점에서는 연구된 바가 없다. 따라서 본 연구에서는 NAC 처리가 가지세포 활성화에 미치는 영향을 재확인하였고, NAC 처리된 가지세포의 T세포 활성 능력 저하, 또는 Th2 반응 유도 여부를 알아보았다. 활성화 시 가지세포에서 증가하는 활성산소기 (reactive oxygen species)는 NAC 처리로 낮아져서, NAC이 가지세포에 항산화작용을 나타냄을 확인하였다. NAC 처리로 가지세포에서 보조자극인자인 CD40과 CD86의 발현이 저해되었으며, 활성화 시 정상적으로 낮아지는 포식기능은 처리된 NAC의 농도에 비례하게 보존되었다. 활성화 시 분비되는 IL-6, IL-10, IL-12는 모두 감소하였다. 이러한 NAC-DC와 함께 배양한 T세포의 증식이나 Th1 cytokine인 IFN-γ, Th2 cytokine인 IL-5의 분비가 모두 저하되어 Th1/Th2의 편중 없이 가지세포의 T세포 자극능력이 전반적으로 감소하였음을 나타내었다. 또한 T세포 배양액에서 IL-10과 TGF-β의 농도 역시 NAC-DC로 자극된 경우에 현저히 줄어서, NAC-DC에 의한 T세포 증식 감소 등은 조절T세포 유도에 의한 것이 아니라 T세포 무반응이 유도된 때문임을 나타내 주었다. N-acetyl-L-cysteine (NAC) is a thiol-containing compound and acts as a precursor for glutathione (GSH). It behaves as an antioxidant in mammalian cells and also exerts anti-inflammatory effects. NAC is also known to affect several immune cells including eosinophils, B cells, T cells, and dendritic cells (DC) in many aspects. Even though it has been reported that NAC inhibits DC activation and shifts the immune response to Th2, these studies exhibit some contradictory results in detail and do not give any information with respect to the induction of regulatory T cells. In this study, we re-analyzed the effects of NAC on DC during their activation. We also evaluated whether it induced T cell anergy, Th1/Th2 shift, or regulatory T cells. NAC suppressed the elevation of intracellular reactive oxygen species during DC activation. In parallel, it down-regulated surface expression of CD40 and CD86, suppressed the decrease of phagocytic function, lowered the secretion of cytokines such as IL-6, IL-10, and IL-12. All these effects showed dose-dependency. Thus, it seems likely that NAC inhibited DC activation with regard to their phenotype and cytokine secretion. When we evaluated the T cell-stimulating capacity of these NAC-DC, T cell proliferation and secretion of both Th1 (IFN-γ) and Th2 cytokine (IL-5) were decreased. This implies that the T cell-stimulating activity of NAC-DC decreased without any shift to Th1 or Th2 cytokine (IL-5). The secretion of IL-10 and TGF-β in the supernatants were also decreased, which suggests that the decrease of T cell proliferation and cytokine secretion is due to the induction of T cell anergy, rather than regulatory T cells.

Effect of high-mobility group box 1 on keratinocytes and fibroblasts

( Chan-yang Lee ),( In-hye Kang ),( Seung-min Oh ),( Jin-woo Lee ),( Young Il Kim ),( Ki-heon Jeong ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: High-mobility group protein B1 (HMGB1) is a physiological activator of immune responses. In patients with chronic inflammatory skin disorders including lupus, atopic dermatitis, and psoriasis, HMGB1 is increased in the cutaneous lesions. Objectives: This study was designed to investigate the effect of HMGB1 on keratinocytes and fibroblasts. Methods: In this study, keratinocytes and fibroblasts were exposed to narrow band ultraviolet B (NBUVB). Thereafter, release of HMGB1 were measured. Then keratinocytes and fibroblasts were treated with recombinant HMGB1 (rHMGB1) and production of inflammatory factors such as interleukin (IL)-1β, IL-6, IL-8, IL-18, chemokine (C-X-C motif) ligand (CXCL)1, CXCL2 and tumor necrosis factor (TNF)-α were examined. Results: 24h after NBUVB irradiation, the level of HMGB1 mRNA was increased in the fibroblasts but it was decreased in the keratinocytes. Extracellular level of HMGB1 was significantly increased in both keratinocytes and fibroblasts, 72h after NBUVB irradiation. After rHMGB1 treatment, proinflammatory molecule such as CXCL-1, IL-6, IL-8 and IL-18 were significantly increased in the keratinocytes and CXCL-1, IL-6 and IL-8 were significantly increased in the fibroblasts. Conclusion: HMGB1 can be released from keratinocytes and fibroblasts by external stress such as NBUVB irradiation and leads to activation of inflammatory signaling pathways in the keratinocytes and fibroblasts.

감껍질 열수 및 초임계 유체 추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),신재영(Jae Young Shin),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.3

본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

Jeong Dong Park,신희석,Sang-Il Lee,A Ram Kim,Jong Moon Park,Sang-Yeop Shin,Jun Hwa Shin,Seung Won Moon,Hyun Park,오민균 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.2

Objective To assess the effi cacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA). Method We used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collageninduced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week)on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for infl ammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue. Results Th ere were no signifi cant diff erences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no diff erences 2 weeks after treatment. Levels of TNF-α, IL-1β, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no diff erences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model. Conclusion Systemic treatment with HPE has no benefi cial eff ects on arthritis in animal models of RA. Th erefore,indiscreet use of HPE in RA should be forbidden.

Effects of the water of yellow soil, Ji-Jang-Soo on cell viability and cytokines production in immune cells

Jeong, Hyun-Ja,Hwang, Gab-Soo,Myung, No-Il,Lee, Joon-Ho,Lee, Ju-Young,Um, Jae-Young,Kim, Hyung-Min,Hong, Seung-Heon Kyung Hee Oriental Medicine Research Center 2006 Oriental pharmacy and experimental medicine Vol.6 No.1

Ji-Jang-Soo (JJS) is known to have a detoxification effect. However, it is still unclear how JJS has these effects in experimental models. In this study, we investigated the effect of JJS on the viability of cells and production of cytokines in human T-cell line, MOLT-4 cells, and human mast cell line, HMC-1 cells. The MOLT-4 cells were cultured for 24 h in the presence or absence of JJS. As the result, JJS (1/100 dilution) significantly increased the cell viability about 78% (P < 0.05) and also increased the interleukin (IL)-2, and interferon $(IFN)-{\gamma}$ production compared with media control at 24 h. But had no effect on IL-4 production. Hypoxia mimic compound, desferroxamine (DFX) decreased the immune cell viability. Cell viability decreased by DFX was increased by JJS. In conclusion, these data indicate that JJS may have an immune-enhancing effect.

들깨(Perilla frutescens) 새싹 추출물의 항산화 및 항염 효과

정승일(Seung-Il Jeong),김현수(Hyeon Soo Kim),전인화(In Hwa Jeon),강현주(Hyun Ju Kang),목지예(Ji Ye Mok),천춘진(Chun Jin Cheon),유현희(Hyeon Hee Yu),정선일(Seon Il Jang) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 들깨 새싹 추출물의 항산화, 항염증 및 항부종에 대한 효과를 조사하였다. 들깨 새싹 추출물은 DPPH와 ABTS 라디칼을 효과적으로 제거하는 항산화 활성이 우수하였다. 또한 들깨 새싹 추출물은 활성화된 설치류 유래 대식세포주인 RAW 264.7세포와 인간 유래 HMC-1 세포의 TNF-α와 IL-1β를 효과적으로 억제하였다. 더욱이 마우스의 귀와 발 부종을 억제하는 우수한 효과가 있었다. 이러한 결과는 들깨 새싹 추출물은 항산화제로 사용될 수 있을 뿐만 아니라 항염증과 항부종에 효과적인 물질이라는 것을 제시해주었다. 이와 관련된 들깨 새싹 추출물의 기능성에 대해서는 앞으로 분자생화학적 수준에서 더 연구해야할 필요성이 있는 것으로 사료된다. We investigated the effects of an ethanol extract from Perilla frutescens sprouts (PFSE) as an antioxidant, and its effects on edema and inflammation in RAW 264.7 cells and HMC-1 cells. The antioxidant activities (DPPH and ABTS radical scavenging) of PFSE were similar to those of butylated hydroxytoluene (BHT) and (±)-6-hydroxy-2,5,7,8- tetramethylchromane-2-carboxylic acid (Trolox). We also investigated the anti-inflammatory effects of PFSE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and HMC-1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) with the calcium ionophore A23187. TNF-α and IL-1β production, which had been increased by treatment with LPS or PMA plus A23187, were significantly inhibited by PFSE in a dose-dependent manner. Furthermore, PFSE significantly reduced the xylene-induced ear edema and the carrageenan-induced paw edema of ICR mice in a dosedependent manner. The effects of PFSE (200 mg/kg) in reducing ear and paw edema were similar to those of aspirin (50mg/kg). These results suggest that PFSE can be potentially used as a medicine for treating oxidative stress, an edematous and inflammatory disease.

P179 : Activin suppresses LPS-induced Toll-like receptors, cytokines, and nitric oxide expression by inhibiting activation of NF-κB and MAPK pathways in normal human melanocytes

( Young Il Kim ),( Seung Won Park ),( Jeong Hwee Choi ),( Myong Il Bae ),( Min Kyung Shin ),( Mu Hyoung Lee ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-β (TGF-β) superfamily. Objectives: To know the mechanism how activin regulates transcription of lipopolysaccharide (LPS)-induced Toll-like receptors (TLRs), cytokines, and inducible nitric oxide synthase (iNOS) in human melanocytes, and the involvement of nuclear transcription factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Methods: Normal human melanocytes were pretreated with activin A before exposure to LPS. Total RNAs were purified and real-time PCR was performed. Also we conducted immunoblot analysis to know the expression levels of proteins. Results: LPS increased mRNA expressions of TLRs (1-10) and cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α), and enhanced mRNA and protein expression of iNOS. Activin inhibited LPS-induced mRNA expressions of TLRs and cytokines, and decreased mRNA and protein expression of LPS-induced iNOS. Also activin suppressed NF-κB p65 activation and blocked IκBα degradation in LPS-stimulated melanocytes, and reduced LPS-induced p38 MAPK and MEK/ERK activations. Conclusion: Activin inhibited expression of genes of TLRs, cytokines, and iNOS in LPS-activated normal human melanocytes. Moreover, anti-inflammatory effect of activin was mediated through suppressing activation of NF-κB and MAPKs signaling pathways in LPS-activated normal human melanocytes, resulting in reduced expression of TLRs, cytokines, and nitric oxide.

Interleukin-2가 호산구 생존에 미치는 영향과 기전에 관한 연구

김효석 ( Hyo Seok Kim ),이영목 ( Young Mok Lee ),최영수 ( Young Soo Choi ),김경호 ( Kyung Ho Kim ),임건일 ( Geon Il Im ),문승혁 ( Jeong Sung Whan ),정성환 ( Moon Seung Hyug ),김현태 ( Hyeon Tae Kim ),어수택 ( Uh Soo Taek ),김용훈 대한결핵 및 호흡기학회 1996 Tuberculosis and Respiratory Diseases Vol.43 No.3

Effect of Feed Selenium-lysine Supplementation on Milk Compositions and Serum Biochemical Indices in Saanen Dairy Goats

Tae-Il Kim,Dong-Hyun Lim,Tai-Young Hur,Seung-Min Ha,Hyun-Jong Kim,Seong-Min Park,Ji-Hoo Park,Sang-Bum Kim,Ji-Hwan Lee,Hyun-Joo Lim,Jeong-Sung Jung,Ha-Yeon Jeong,Jay Lee,Kwang-Seok Ki,Vijayakumar Mayak 경상대학교 농업생명과학연구원 2019 농업생명과학연구 Vol.53 No.4

An experiment was carried out to assess the effect of feed selenium-lysine (Se-Lys) supplementation on milk compositions and serum biochemical indices in Saanen dairy goats in Korea. A total of twelve 36 months old Saanen lactating dairy goats (47±6.21 kg) fed the similar dry matter intake twice a day at 2% of BW (DMI) (10.9% moisture of concentrate and 19% moisture of roughage), milk yield (2.5 kg/d) and parity (2) were randomly selected and subjected for the present study, divided into two groups with six goats in each group. The goats in the control group received rice hulls (10 g/ day) only, and did not receive Se-Lys; goats in the treatment group were fed 0.06 g of Se-Lys with 10 g of rice hulls every day before feeding roughage for six weeks. The milk sample was collected every week, and its compositions were analyzed. The results of the present study showed that there is no significantly increased milk production in Se-Lys treated group goats when compared with control group goats. But, Se-Lys treatment significantly increased the milk protein content (3.98±0.16%), fat (3.72±0.27%), lactose (4.07±0.14%), total solids (12.51±0.28%) and urea (14.42±1.45 mg/dl) content as compared to the control group goats (p<0.05). The somatic cell counts (207,740±28.81 cells/ml) were significantly lower in the Se-Lys treated group than in the control group (p<0.05). Also, the results of the current study showed that supplementation of Se-Lys were significantly decreased the blood biochemical indices of IL-6 (34.34±6.04 pg/ml), TNT-α (0.56±0.22 ng/ml), MDA (5.07±1.03 ng/ml), GPx-1 (9.07±5.17 ng/ml), sCD4 (2.64±1.02 ng/ml) and sCD8 (5.08±2.08 ng/ml) level when compared with without addition of Se-Lys group dairy goats (p<0.05). On the other hand, the selenoprotein P (1,580.18±127.62 ng/ml) level was significantly higher in Se-Lys supplemented group than in the control group (p<0.05). Based on the study results, it was concluded that feed Se-Lys supplementation may improve milk yield with positively improved protein, fat, lactose, total solids, urea content, and biochemical indices without negative effects on milk production traits.