GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma

이규,이창민,정인덕,정영일,천성학,박희주,최일환,안순철,신용규,이상율,염석란,김종석,박영민,Lee, Kyu,Lee, Chang-Min,Jung, In-Duk,Jeong, Young-Il,Chun, Sung-Hak,Park, Hee-Ju,Choi, Il-Whan,Ahn, Soon-Cheol,Shin, Yong-Kyoo,Lee, Sang-Yull,Yeom, S Korean Society of Life Science 2007 생명과학회지 Vol.17 No.8

Myristicin은 육두구에서 발견되는 고농축 정유 중 하나인 물질이다. 하지만 Th1/Th2 면역반응에서 육두구의 항알레르기 효과는 아직 밝혀지지 않았다. 최근에 Th1/Th2 전사인자로서 T-bet, GATA-3가 밝혀졌는데 이번 실험에서 myristicin이 ovalbumin(OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1,Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다. 또한 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 myristicin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 myristicin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 myristicin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

만성 간염에서 Interleukin-6의 간내발현

김성숙(Sung Sook Kim),김도영(Doe Young Kim),문일환(Il Whan Moon),변광호(Kwang Ho Pyun),최인표(In Pyo Choi) 대한소화기학회 1995 대한소화기학회지 Vol.27 No.4

N/A Rackground/Aims: Interleukin-6 (lL-6), also known as B cell stimulatory factor 2(BSF-2), induces the final maturation of B cells to antitxxiy-producing cells. IL-6 has many biologic properties including the immune and intlammatory responses. This study wos aimed to evaluate the role of local interleukin 6(IL-6) in the pathogenesis of chronic hepatitis. Methods; We examined the cellular site and grade of IL-6 staining in paraffin sections of the liver from 24 patients with liver disease, using immunohistochemistry with a polyclonal antitwdy. The patient. Were divided into two groups; Group A(n=l3) with high histologic uctivi1y consisted of CAH-type B(n=10) ond active cirrhosis(n=3), whilc Group B(n= l l) with low hi.itologic activity consisted of CPH-type B(n=4), inactive cirrhosis(n=2) and fatty liver(n=S). Results: There was no staining of IL-6 in normal liver tissue. Thv grade.I of IL-6 staining in Group A were three positive in seven cases (53.81o), two positive in five ca.ics(38.3%) and one positive in only one case(7.7%), while those in Group B were one positivc in three cases(27.3%) ancl trace in eight case.(72.7ln). IL-6 stained cells in chronic hepatitis were hepatocytcs, cspecially in the areu ot' piecemeol necrosi.I, bilc duct cel1., infiltrating inflammatory cells and endothelial cell.I. The score of histological activity index(HAJ), piecemeal necrosis and fibrasis and thc gradv. Of 1L-6 staining of Group A were ull significantly higher than those of Group B. The grade of IL-6 staining and HAI werc well correlated(r =0.74, p 0.0l), Conclusion: Locally produced IL-6 in the liver may contribute to the inflammatory process and immunological response in chronic hepatiti.. (Korean 3 Gastroenterol 1995;27:403-411)

류마티스 관절염환자의 혈청 Interleukin-10

유빈 ( Bin Yoo ),박재경 ( Jae Kyoung Park ),오원일 ( Won Il Oh ),오순환 ( Sun Whan Oh ),문희범 ( Hee Bom Moon ) 대한류마티스학회 1997 대한류마티스학회지 Vol.4 No.1

Objective: To investigate whether the serum levels of IL-10 in patients with rheumatoid arthritis are different from those of normal controls and SLE patients and to find out any correlation with disease activity parameters of rheumatoid arthritis. Methods: Sera from 20 healthy normal persons, 16 rheumatoid arthritis patients and 16 patients with systemic lupus erythematosus were collected and measured for IL-10 and IL-6. Various disease activity parameters were measured in RA patients. Results: The serum level of IL-10 in RA patients was significantly elevated compared to normal controls but lower than those of SLE patients. In RA patients there was no definite correlation between the disease activity parameters and serum IL-10 levels. Despite significant improvements in terms of various disease activity parameters, there was no significant change of serum IL-10 levels after treatment in RA patients. In seropositive RA patients, positive correlation was found between serun IL-10 and rheumatoid factor levels. Conclusion: Our findings show that the serum IL-10 levels in patietns with RA are elevated compared to normal controls but lower than those of SLE patients. There was no correlation between serum IL-l0 levels and disease acivity parameters of RA.

Caffeic acid phenethyl ester inhibits the inflammatory effects of interleukin-1β in human corneal fibroblasts

Yang, Jae-Wook,Jung, Won-Kyo,Lee, Chang-Min,Yea, Sung Su,Choi, Yung Hyun,Kim, Gi-Young,Lee, Dae-Sung,Na, Giyoun,Park, Sae-Gwang,Seo, Su-Kil,Choi, Jung Sik,Lee, Young-Min,Park, Won Sun,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY Vol.36 No.5

<P><I>Context</I>: Expression of various inflammatory mediators in corneal fibroblasts contributes to corneal inflammation.</P><P><I>Objective</I>: The purpose of this study was to assess the possible effects of caffeic acid phenethyl ester (CAPE) on the expression of inflammatory mediators during an inflammatory response in human corneal fibroblasts.</P><P><I>Materials and methods</I>: The levels of interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule-1 (ICAM-1) from IL-1β-exposed human corneal fibroblasts were measured with enzyme-linked immunosorbent assays (ELISA). The regulatory mechanisms of CAPE on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. A functional validation was carried out by evaluating the inhibitory effects of CAPE on neutrophil and monocyte migration <I>in vitro</I>.</P><P><I>Results</I>: CAPE inhibited the expression of IL-6, MCP-1 and ICAM-1 induced by the pro-inflammatory cytokine IL-1β in corneal fibroblasts. The activation of AKT and NF-κB by IL-1β was markedly inhibited by CAPE, whereas the activity of mitogen-activated protein kinases (MAPKs) was not affected. CAPE significantly suppressed the IL-1β-induced migration of differentiated (d)HL-60 and THP-1 cells.</P><P><I>Discussion</I>: These anti-inflammatory effects of CAPE may be expected to inhibit the infiltration of leukocytes into the corneal stroma <I>in vivo</I>.</P>

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

Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages

Ryu, BoMi,Choi, Il-Whan,Qian, Zhong-Ji,Heo, Soo-Jin,Kang, Do-Hyung,Oh, Chulhong,Jeon, You-Jin,Jang, Chul Ho,Park, Won Sun,Kang, Kyong-Hwa,Je, Jae-Young,Kim, Se-Kwon,Kim, Young-Mog,Ko, Seok-Chun,Kim, G The Korean Society of Phycology 2014 ALGAE Vol.29 No.4

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

FK506과 cyclosporin A가 기관지상피세포, 단핵구, 림프구 및 폐포대식세포에서 $I{\kappa}B{\alpha}$ 분해 및 $IKK{\alpha}$ 활성에 미치는 효과

윤호일,이창훈,이희석,이춘택,김영환,한성구,심영수,유철규,Yoon, Ho Il,Lee, Chang-Hoon,Lee, Hee-Seok,Lee, Choon-Taek,Kim, Young Whan,Han, Sung Koo,Shim, Young-Soo,Yoo, Chul-Gyu 대한결핵및호흡기학회 2003 Tuberculosis and Respiratory Diseases Vol.54 No.4

연구배경 : Cyclosporin A(CsA)와 tacrolimus(FK506)은 현재 임상에서 널리 쓰이는 면역억제제이다. CsA와 FK506이 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 영향에는 세포에 따라 다양한 효과가 알려져 있다. 그러나 CsA와 FK506이 기관지 상피세포에서 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 효과에 관해서는 알려져 있지 않고, 각종 염증 세포에서의 차이에 관해서도 보고가 미미한 실정이다. 본 연구에서는 비염증세포인 기관지상피세포와, 폐의 염증에 중요한 역할을 하는 염증 세포(폐포대식세포, 단핵구, 림프구)에서 CsA와 FK506이 $I{\kappa}B{\alpha}$의 분해에 미치는 영향과 그 기전을 평가하였다. 방 법 : 비염증세포로는 BEAS-2B와 A549 세포주를 이용하였다. FK506 또는 CsA 전처치 후 TNF-${\alpha}$로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. 염증세포로는 폐포대식세포, 말초혈액 단핵구 및 림프구를 이용하였고, 역시 FK506 또는 CsA 전처치 후 TNF-${\alpha}$, IL-$1{\beta}$, LPS로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. IKK의 활성도는 GST-$I{\kappa}B{\alpha}$를 기질로 이용한 in vitro immune complex kinase assay로 평가하였다. 결 과 : 사용된 모든 세포에서 CsA와 FK506은 $I{\kappa}B{\alpha}$의 발현에 영향을 미치지 않았다. 기관지 상피세포에서 TNF-${\alpha}$ 자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA의 전처치로 억제되었으나, FK506의 전처치로는 억제되지 않았다. 단핵구, 림프구 및 폐포대식세포에서 외부자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA 또는 FK506의 전처치로 억제되었으나 IKK활성은 억제되지 않았다. 결 론 : CsA와 FK506은 각각 기관지 상피세포와 단핵구, 림프구, 폐포대식세포에서 외부 자극에 의한 $I{\kappa}B{\alpha}$의 분해를 억제하는데, 이는 IKK 활성화의 억제가 아닌 다른 경로를 통하는 것으로 생각된다. Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model

Lee, Hye-Rim,Shon, Oog-Jin,Park, Se-Il,Kim, Han-Jun,Kim, Sukyoung,Ahn, Myun-Whan,Do, Sun Hee MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.1

<P>Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(−), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(−) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, <I>i.e.</I>, PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP <I>in vivo</I>. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an <I>in vivo</I> meniscus injury accelerates fibrosis, instead of meniscal cartilage.</P>

후코이단에 의한 인간 폐 섬유모세포의 활성 억제 효과

임미진 ( Mi-jin Yim ),이대성 ( Dae-sung Lee ),최그레이스 ( Grace Choi ),이정민 ( Jeong Min Lee ),최일환 ( Il-whan Choi ) 한국수산과학회(구 한국수산학회) 2016 한국수산과학회지 Vol.49 No.6

Fucoidan, one of the dominant sulfated polysaccharides extracted from brown seaweed, possesses a wide range of biological activities. Transforming growth factor-β (TGF-β) plays a pivotal role in the pathogenesis of pulmonary fibrosis, by stimulating the synthesis of profibrotic factors. In this study, we investigated the in vitro effects of fucoidan on collagen synthesis, α-smooth muscle actin (α-SMA) expression, and interleukin (IL)-6 production in TGF-β-stimulated human pulmonary fibroblasts. The expression of type I collagen and α-SMA was detected by Western blot, and the production of IL-6 by enzyme-linked immunosorbent assay. TGF-β1 treatment of pulmonary fibroblasts enhanced the expression of α-SMA, type I collagen, and IL-6 whereas these effects were inhibited in cells pretreated with fucoidan. The activation of Smad2/3, p38 mitogen-activated protein kinases (MAPKs), and Akt was also inhibited in fucoidan-pretreated, TGF-β1-stimulated human pulmonary fibroblasts. These data demonstrate the anti-fibrotic potential of fucoidan in TGF-β-induced human pulmonary fibroblasts, via the inhibition of Smad2/3, p38 MAPKs, and Akt phosphorylation. Our results suggest the therapeutic potential of fucoidan in the prevention or treatment of pulmonary fibrosis.

Sargassum horneri inhibits psoriasis-related inflammation in HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesions in mice

Mi-Jin Yim,Jeongmin Lee,Seok-Chun Ko,Hyun-Soo Kim,Jeong Min Shin,Ji Yul Kim,Dae-Sung Lee,Il-Whan Choi 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Sargassum horneri exhibits broad bioactive properties. However the anti-psoriatic effects of its have not been reported. The present study evaluated whether ethanol extract of S. horneri (ESH) can improve the symptoms of psoriasis in vitro and in vivo and elucidated the mechanisms underlying those effects in vitro. ESH treatment significantly attenuated the protein levels of IL-6, IL-8, and TNF-α in IFN-γ/TNF-α stimulated HaCaT keratinocytes. In addition, ESH inhibited (PI3K)/Akt phosphorylation and NF-κB activation in HaCaT keratinocytes. We further demonstrated that the ESH significantly ameliorates the severity of skin lesions (erythema, scaling, and thickness) in the IMQ-induced psoriasis-like mouse model. ESH attenuated the production of inflammatory cytokines by inhibiting Akt/NF-κB signaling pathways in IFN-γ/TNF-α-induced HaCaT keratinocytes. Furthermore, ESH could ameliorate the severity of skin lesions in an IMQ-induced psoriasis-like mouse model. Thus, S. horneri has considerable potential in the treatment or prevention of inflammatory disorders, such as psoriasis.