DBA/1JCrj Mouse에 있어서 콜라젠유도관절염에 관한 면역학적 고찰

박승규,이지연,정일엽,최용경,최인성,김효준 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

There is growing evidence that a variety of cytokines are secreted by cells at the inflammation sites of rheumatoid arthritis (RA) and that CDS+ B cell, a minor subtype of B cell population producing natural autoantibodies, is implicated in pathogenesis of RA. In this study, we evaluated the both cytokne levels and change of CDS+ B cell population in the peripheral blood from DBA/lJCrj mice(H-2`) which are collagen-induced arthritis(CIA) susceptible strain. Surprisingly, the healthy DBA/1JCrj and MRL/Ipr/Ipr(H-2'`) mice which were autoimmune susceptible strains tested in this experiment, showed lower IL-4, IL-6 and IL-10 levels in serum by 60% than heal-thy normal mouse strains such as Balb/c(H-2d), C57BL/6(H-2') and outbred ICR mice. MRL/lpr/ 1pr mice in which onset of spontaneous autoimmune disease is dependent upon age were similar to healthy DBA/1JCrj mice in levels of the cytokines in the serum when they are young. After the CIA(for DBA/1JCrj) or the spontaneous autoimmune disease(for MRL/lpr/Ipr) had been developed in the susceptible mouse strains, the levels of IL-6 and IL-4 in the serum were increased to 1.8- and 13-fold, respectively, as compaired with those from control groups while level of IL-10 remained relatively constant. The elevated levels of IL-4- and IL-6, however, in the serum from mice with disease status were still below those of the healthy normal mouse strains. On the other hand, CDS+ B cell population in the peripheral blood, which were reported to be increased with the development of RA for human, was rather significantly decreased for the CIA-induced DBA/lJCrj mice as evidenced by FACS analysis. It could be due to the differences in the pathogenic mechanism between CIA and RA. Taken together, our results. suggest that the levels of both these cytokines and CDS+ B cells may be utilized as important diagnostic markers for arthritides.

Genetic effect of <i>CCR3</i> and <i>IL5RA</i> gene polymorphisms on eosinophilia in asthmatic patients

Lee, June-Hyuk,Chang, Hun Soo,Kim, Ji Hyun,Park, Se-Min,Lee, Yong Mok,Uh, Soo Taek,Rhim, Taiyoun,Chung, Il Yup,Kim, Yong-Hoon,Park, Byung Lae,Park, Choon-Sik,Shin, Hyoung Doo Elsevier 2007 The journal of allergy and clinical immunology Vol.120 No.5

<P><B>Background</B></P><P>Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.</P><P><B>Objective</B></P><P>We investigated the association of polymorphisms in <I>CCR3</I> and <I>IL5RA</I> with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.</P><P><B>Methods</B></P><P>Polymorphisms in <I>CCR3</I> and <I>IL5RA</I> were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor α (IL-5Rα) protein expression on eosinophils was measured by means of flow cytometry.</P><P><B>Results</B></P><P>Although polymorphisms in <I>CCR3</I> were not associated with asthma susceptibility, the <I>CCR3</I> haplotype <I>ht2</I> showed a negative gene dose effect on the eosinophil count (<I>P</I> = .003–.009). <I>IL5RA c.−5091G>A</I> was weakly associated with eosinophil count. The effects of <I>ht2</I> were greater when paired with <I>IL5RA c.−5091A</I> (<I>P</I> = .001–.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without <I>ht2</I> than in those with <I>ht2</I>. Asthmatic patients with the <I>IL5RA c.−5091A</I> allele showed higher IL-5Rα expression than those who were homozygous for the G allele.</P><P><B>Conclusion</B></P><P>The genetic association between <I>CCR3</I> polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the <I>CCR3</I> polymorphisms were paired with polymorphisms in <I>IL5RA</I>. The protein expression levels of CCR3 and IL-5Rα on peripheral blood eosinophils are associated with the polymorphisms on their own genes.</P><P><B>Clinical implications</B></P><P>The identification of single nucleotide polymorphisms and haplotypes of <I>CCR3</I> and <I>IL5RA</I> might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.</P>

Anti-inflammatory Activity of an Ethanol Extract of Caesalpinia sappan L. in LPS-induced RAW 264.7 Cells

Il Yun Jeong,Chang Hyun Jin,Yong Dae Park,Hyo Jung Lee,Dae Seong Choi,Myung Woo Byun,Yeung Ji Kim 한국식품영양과학회 2008 Preventive Nutrition and Food Science Vol.13 No.4

The anti-inflammatory activities of an ethanol extract of Caesalpinia sappan L. (CS) were investigated in LPS-induced RAW 264.7 cells. Result indicated that CS inhibited the LPS-induced NO production in a dose-dependent manner with an IC?? of 10.9 ㎍/mL. In addition, CS attenuated the iNOS mRNA and protein expression by inhibiting NF-κB activation. CS also suppressed the productions of IL-6 and MCP-1 in a dose-dependent manner, with IC?? values of 15.9 ㎍/mL and 5.47 ㎍/mL, respectively. In addition to the anti-inflammatory activities, CS decreased intracellular ROS formation in the same cells. In conclusion, CS inhibited the production of NO, IL-6 and MCP-1 via a suppression of the NF-κB activation and intracellular ROS generation.

Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory Response <i>In Vitro</i> and <i>In Vivo</i>

Cha, Ji Young,Jung, Ji Yun,Jung, Jae Yup,Lee, Jong Rok,Cho, Il Je,Ku, Sae Kwang,Byun, Sung Hui,Ahn, Yong-Tae,Lee, Chul Won,Kim, Sang Chan,An, Won G. Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-<I><I>α</I></I> (TNF-<I><I>α</I></I>)) and nuclear factor-kappa B (NF-<I><I>κ</I></I>B) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-<I><I>κ</I></I>B, and MAPKs as well as production of prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), nitric oxide (NO), IL-6, and TNF-<I><I>α</I></I> induced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-<I><I>κ</I></I>B and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-<I><I>α</I></I>. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWS <I>in vitro</I> and <I>in vivo</I>.</P>

Anti-inflammatory Activity of an Ethanol Extract of Caesalpinia sappan L. in LPS-induced RAW 264.7 Cells

Jeong, Il-Yun,Jin, Chang-Hyun,Park, Yong-Dae,Lee, Hyo-Jung,Choi, Dae-Seong,Byun, Myung-Woo,Kim, Yeung-Ji The Korean Society of Food Science and Nutrition 2008 Preventive Nutrition and Food Science Vol.13 No.4

The anti-inflammatory activities of an ethanol extract of Caesalpinia sappan L. (CS) were investigated in LPS-induced RAW 264.7 cells. Result indicated that CS inhibited the LPS-induced NO production in a dose-dependent manner with an $IC_{50}$ of $10.9\;{\mu}g/mL$. In addition, CS attenuated the iNOS mRNA and protein expression by inhibiting NF-${\kappa}B$ activation. CS also suppressed the productions of IL-6 and MCP-1 in a dose-dependent manner, with $IC_{50}$ values of $15.9\;{\mu}g/mL$ and $5.47\;{\mu}g/mL$, respectively. In addition to the anti-inflammatory activities, CS decreased intracellular ROS formation in the same cells. In conclusion, CS inhibited the production of NO, IL-6 and MCP-1 via a suppression of the NF-${\kappa}B$ activation and intracellular ROS generation.

The effects of BRL-50481 on ovalbumin-induced asthmatic lung infl ammation exacerbated by co-exposure to Asian sand dust in the murine model

Hong Jo Kim,Jin Yong Song,Tae Il Park,Won Seok Choi,Jong Heon Kim,Oh Seong Kwon,Ji-Yun Lee 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.1

Asian sand dust (ASD), which mainly originatesin China and Mongolia in the spring and blows into Korea,can exacerbate respiratory and immunological diseases. This study aims to observe eff ects of co-exposure to ASD onovalbumin (OVA)-induced asthmatic lung infl ammation andof treatment with a phosphodiesterase 7 (PDE7) inhibitor ina mouse model. The challenge with OVA increased airwayhyperresponsiveness (AHR) and infl ammatory cell infi ltrationinto the lung tissue. Interleukin (IL)-13, tumor necrosisfactor-alpha, monocyte-protein-1, mucin, and antigen-specific IgE and IgG1 production increased in mouse serum. The co-exposure of ASD signifi cantly exacerbated theseeff ects in this asthma model. Notably, the administration ofa PDE7 inhibitor, BRL-50481 (BRL), signifi cantly reducedAHR, infi ltration of infl ammatory cells into the lungs, andthe levels of type 2 T helper cell-related cytokines, antigenspecific immunoglobulins, and mucin. Thus, the administrationof BRL ameliorated OVA-induced allergic asthmaticresponses exacerbated by co-exposure to ASD. This studysuggests that PDE7 inhibition can be a therapeutic strategyfor infl ammatory lung diseases and asthma via the regulation of T lymphocytes and reduction of IL-13, and, consequently,mucin production.

Anti-inflammatory Effects of Low-molecular Weight Chitosan Oligosaccharides in IgE-antigen Complex-stimulated RBL-2H3 Cells and Asthma Model Mice

Mi Ja Chung,Jae Kweon Park,Ji Sun Lee,Seul Lee,Yong Il Park 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides (LM-COS) prepared from high-molecular weight chitosan by enzymatic digestion were investigated against allergic reaction and allergic asthma in vivo and in vitro. Allergic asthma is an inflammatory disease of the airways associated with enhanced degranulation and cytokine generation. The LM-COS (<1 kDa), consisting of glucosamine (GlcN)n, n = 3-5, were capable of inhibiting both antigen-stimulated degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. The protective effect of LM-COS against ovalbumin (OVA)-induced lung inflammation in asthma model mice was also examined. Oral administration of LM-COS (16 mg/kg body weight/day) resulted in a significant reduction in both mRNA and protein levels of interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor (TNF)-αin the lung tissue and bronchoalveolar lavage fluid (BALF). The protein levels of IL-4, IL-13 and TNF-αin BALF were decreased by 5.8-fold, 3.0-fold and 9.9-fold, respectively, compared to those in the OVA-sensitized/challenged asthma control group. These results suggest that oral administration of LM-COS is effective in alleviating the allergic inflammation in vivo and thus can be a good source material for the development of a potent therapeutic agent against mast cell-mediated allergic inflammatory responses and airway inflammation in allergic inflammatory diseases, including asthma.

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.

검정콩 껍질 유래 안토시아닌의 RBL-2H3 세포에서 탈과립화와 사이토카인 생성 저해 효과

정미자(Mi Ja Chung),하태정(Tae Joung Ha),최하나(Ha Na Choi),이지선(Ji Sun Lee),박용일(Yong Il Park) 한국식품영양과학회 2011 한국식품영양과학회지 Vol.40 No.12

안토시아닌(anthocyanins)은 플라보노이드에 속하고 항산화 활성들을 포함한 그들의 다양한 건강 유익성에 대해 알려져 있다. 그들 중 검정콩 껍질에서 분리한 주요 안토시아닌은 glycopyranose를 함유하고 있는 배당체이다. 천식은 호염기성 세포(basophils)와 비만세포(mast cells)를 포함한 다양한 면역세포와 관련된 알레르기 관련 질병이다. 호산구 (eosinophils), 호염기성 세포, 비만세포는 탈과립화에 의한 천식-특이적 보조 2(T-helper 2) 사이토카인 분비 그리고 계속해서 일어나는 증폭과 같은 염증을 일으키는 매개체의 증가를 통해 알레르기 천식(allergic asthma)에서 중요한 역할을 한다. 흰쥐 호염기성 백혈병(rat basophilic leukemia) RBL-2H3 세포는 알레르기 반응을 측정하기 위해 가장 일반적으로 사용되는 in vitro 모델이다. 본 연구에서는 검정콩 껍질 안토시아닌이 항원으로 자극한 RBL-2H3 세포에서 탈 과립 그리고 Th2 사이토카인 생산에 미치는 효과를 조사하였다. 세포 탈과립은 β-hexosaminidase의 방출을 검출함으로써 평가하였다. IgE-항원 복합체로 자극한 RBL-2H3 세포내 β-hexosaminidase 방출과 Th2 사이토카인 생산이 무 처리군의 그것과 비교하여 더 높았다. 안토시아닌은 RBL-2H3 세포의 IgE-항원 복합체 유도 탈과립을 현저하게 억제 시켰고 RBL-2H3 세포내 IgE-항원 복합체-매개체 interleukin( IL)-4, IL-13 그리고 TNF-α 생산을 저해하였다. 이러한 결과는 검정콩 껍질 유래 안토시아닌이 알레르기 반응(allergic reaction)을 현저히 저해하는 효과가 있음을 보였고, 이들 안토시아닌이 향후 알레르기 천식을 억제하거나 개선하는데 유용한 물질로 사용될 가능성이 있을 것으로 판단되었다. Anthocyanins belong to a group of flavonoid compounds and are well known for their various health beneficial effects, which include antioxidative activities. Among them, the major anthocyanins isolated from seed coat of black soybean (Glycine max L.) were previously characterized as glycosides containing glucopyranose. Asthma is an allergic disease that is strongly associated with various immune cells, including basophils and mast cells. Eosinophils, basophils, and mast cells play important roles in allergic asthma through the release of inflammatory mediators such as asthma-specific T-helper 2 (Th2) cytokines and subsequent amplification of asthma symptoms via degranulation. Rat basophilic leukemia RBL-2H3 cells are the most common in vitro models for evaluating allergic reactions. In this study, we examined the effects of anthocyanin from seed coat of black soybean on antigen-stimulated degranulation and Th2 cytokine production in RBL-2H3 cells. Cell degranulation was evaluated by measuring the release of β-hexosaminidase. β-Hexosaminidase release and Th2 cytokine production in RBL-2H3 cells was much higher upon stimulation with IgE-antigen complex than those in untreated control cells. Anthocyanins significantly suppressed IgE-antigen complex-induced degranulation of RBL-2H3 cells and inhibited IgE-antigen complex-mediated interleukin (IL)-4, IL-13, and tumor necrosis factor α (TNF-α) production in RBL-2H3 cells. These findings suggest that anthocyanins from seed coat of black soybean effectively inhibit allergic reactions and may have beneficial effects against allergic asthma.

Structure and Immune Modulating Activity of a Polysaccharide Purified from Mulberry Fruits Pericarp

Ji Sun Lee,Andriy Synytsya,Hyun Bok Kim,Woo Jung Kim,Seong Jae Jang,Mi Ja Chung,Ju Hee Ko,Doo Jin Choi,Ha Na Choi,Yong Il Park 한국당과학회 2011 한국당과학회 학술대회 Vol.2011 No.1

In the present study, we investigated structure and immune modulating activity of a polysaccharide (tentatively named JS-MP-1), previously purified from Mulberry fruits (Morus bombycis Koidz) pericarp. Based on HPAEC-PAD analysis, major monosaccharides of JS-MP-1 were shown to be galactose (37.6% in mole percentage), arabinose (36.3%) and rhamnose (18.4%), respectively. EA analysis did not show the presence of sulfur (0.07%). Biochemical analysis showed neutral sugars (35.25%), uronic acid (11.25%), sulfate (0.16%) and proteins (0.3%). FT-IR spectra of JS-MP1 confirmed the presence of carboxyl groups (uronic acid – α-GalAp in RG1) and COC, CO and CC stretching vibrations at 948 – 1150 cm-1 corresponding to polysaccharides. Peak at 894 cm-1 indicates the presence of β-Galp units. 1H-NMR spectrum (in D2O) confirmed the presence of α-1,2-Rhap, α-Araf, β -Galp and α-1,4-GalAp units. The most intense HMQS signals were observed for terminal α-Araf. The presence of methylester groups in the residues of α -1,4-GalAp was confirmed by the HMQS peak at C 54.3/H 4.01 ppm (OCH3). Taken collectively, the JS-MP-1 is probably a rhamnogalacturonan type 1 (RG1), which contains: (a) partially methyl esterified α-1,4-D-GalAp and α -1,2-L-Rhap units in backbone, and (b) α-L-Araf and β-Galp are bound to Rha as terminal units or more complex side chains (arabinan, galactan and/or arabinogalactan). The ELISA assay showed that JS-MP-1 remarkably stimulates the release of the proinflammatory cytokines, TNF-α and IL-6, in a dose-dependent manner, from the RAW 264.7 cells. RT-PCR analysis also showed a significant induction of the iNOS and COX-2 gene expression. These results suggest that JS-MP-1 isolated from the Mulberry fruits has immune modulating activities.