Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands

Kang, Kwi Young,Kim, Hyun-Ok,Kwok, Seung-Ki,Ju, Ji Hyeon,Park, Kyung-Su,Sun, Dong-Il,Jhun, Joo Yeon,Oh, Hye Jwa,Park, Sung-Hwan,Kim, Ho-Youn BioMed Central 2011 ARTHRITIS RESEARCH AND THERAPY Vol.13 No.5

<P><B>Introduction</B></P><P>Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.</P><P><B>Methods</B></P><P>Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.</P><P><B>Results</B></P><P>Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.</P><P><B>Conclusions</B></P><P>Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.</P>

Chronological changes in inflammatory cytokines immunoreactivities in the mouse hippocampus after systemic administration of high dosage of tetanus toxin.

Yan, Bing Chun,Park, Joon Ha,Kim, In Hye,Shin, Bich Na,Ahn, Ji Hyeon,Yoo, Ki-Yeon,Lee, Deuk-Sik,Kim, Myong Jo,Kang, Il-Jun,Won, Moo-Ho Springer-Verlag 2012 Experimental brain research Vol.223 No.2

<P>Tetanus toxin (TeT) is an exotoxin and has a capacity for neuronal binding and internalization. In the present study, we compared changes in the immunoreactivities and protein levels of interleukin (IL-) 2 as a pro-inflammatory cytokine and IL-4 as an anti-inflammatory cytokine in the hippocampus proper (HP) and dentate gyrus (DG) after systemic treatment of 10 or 100?ng/kg TeT into mice. In this study, we could not find any neuronal damage or loss in any subregions of the hippocampus after TeT treatment. In the control groups, strong IL-2 immunoreactivity was shown in the stratum pyramidal (SP) of the HP and in the granule cell layer (GCL) of the DG. At 6?h post-treatment, IL-2 immunoreactivity was hardly detected in the SP and GCL; however, strong IL-2 immunoreactivity was shown in the stratum oriens of the HP in both the groups. Thereafter, intermediate IL-2 immunoreactivity was shown in the SP and GCL. On the other hand, intermediate IL-4 immunoreactivity was detected in the SP and GCL of the control groups. At 6?h post-treatment, IL-4 immunoreactivity in the SP and GCL was apparently increased. Thereafter, IL-4 immunoreactivity was lower than that at 6?h post-treatment. In brief, IL-2 and 4 immunoreactivities were easily detected in SP and GCL in the controls and dramatically decreased and increased at 6?h post-treatment, respectively.</P>

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol.26 No.4

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</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

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

Lee, Hyeon Il,Kim, Mee Kum,Oh, Joo Youn,Ko, Jung Hwa,Lee, Hyun Ju,Wee, Won Ryang,Lee, Jin Hak The Korean Academy of Medical Sciences 2008 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.23 No.3

<P>We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-γ in cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00±1.96 days, which showed no statistical differences compared with that of control (8.00±1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-γ markedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.</P>

대강활탕(大羌活湯)이 Collagen으로 유발된 관절염의 발생 및 치료에 미치는 영향

정수현 ( Su Hyeon Jeong ),김순중 ( Sung Jung Kim ),서일복 ( Il Bok Seo ) 한방재활의학과학회 2004 한방재활의학과학회지 Vol.14 No.3

Objectives: This study was carried out to investigate the anti-pathogenetic and curative effects of Taeganghwal-tang(Daqianghuo-tang) on collagen-induced arthritis in Wistar rats. Methods: Experiment 1; Thirty male rats were divided into non-treated normal group, porcine type II collagen immunized control group, and collagen immunized and treated group medicated with extract of Taeganghwal-tang(Daqianghuo-tang) for 15days after collagen immunization. Body weight, paw edema volume, and thickness of ankle joint were measured at 0, 10, 15days after immunization. Arthritic score was evaluated at 11, 12, 13, 14, 15days after immunization. At 15days after immunization, the incidence of arthritis was evaluated, and serum TNF-α, IL-1β and anti-collagen IgG level were analysed, and histopathological examination was performed on the ankle joint. Experiment 2; Thirteen rats, that were shown the gross lesions of collagen-induced arthritis, were divided into control group and treated group medicated with extract of Taeganghwal-tang(Daqianghuo-tang) for 15days after onset of arthritis. Non immunized seven rats were served as normal group. Body weight, paw edema volume, and thickness of ankle joint were measured at 0, 5, 10, 15days after treatment. At 15days after treatment, serum TNF-α, IL-1β and anti-collagen IgG level were analysed, and histopathological examination was performed on the ankle joint. Results: Experiment 1; -. Incidence of arthritis was 60% in control group and 10% in treated group. -. Arthritic score of treated group(0.3±0.9 at 13days, 0.3±0.9 at 14days, 0.3±0.9 at 15days) was significantly decreased(P<0.01) compared with control group(3.0±2.7 at 13days, 3.61±3.1 at 14days, 3.9±3.4 at 15days) respectively. -. Paw edema volume(㎖) of treated group(1.90±0.11) was significantly decreased(P<0.01) compared with control group(2.55±0.53) at 15days after immunization. -.Thickness of ankle joint(㎜) of treated group(6.64±0.15) was significantly decreased(P<0.01) compared with control group(8.35±1.75) at 15days after immunization.-.Serum TNF-α level(pg/㎖) of treated group(46.00±25.90) was significantly decreased(P<0.05) compared with control group(97.52±49.97) at 15days after immunization.-.Serum IL-1β level(pg/㎖) of treated group(39.40±10.42) was significantly decreased(P<0.05) compared with control group(52.22±15.32) at 15days after immunization.-.Serum anti-collagen IgG level(㎎/㎖) of treated group(0.27±0.16) was significantly decreased(P<0.05) compared with control group(0.47±0.20) at 15days after immunization. Experiment 2; -.Paw edema volume(㎖) of treated group(3.12±0.28 at 10days, 3.12±0.27 at 15days) was significantly decreased(P<0.05) compared with control group( 3.72±0.49 at 10days, 3.62±0.48 at 15days) respectively.-.Serum TNF-α level(pg/㎖) of treated group(84.64±22.04) was significantly decreased(P<0.05) compared with control group(135.31±55.56) at 15days after treatment.-.Serum IL-1β level(pg/㎖) of treated group(58.16±7.28) was not significantly different compared with control group(66.75±10.68) at 15days after treatment.-.Serum anti-collagen IgG level(㎎/㎖) of treated group(0.78±0.09) was not significantly different compared with control group(0.87±0.08) at 15days after treatment.-.Histopathologically, destructive lesions of articular cartilage and subchondral bony tissue, and degree of fibrous ankylosis in treated group were alleviated compared with those of control group at 15 days after treatment. Conclusions: These results indicated that Taeganghwal-tang(Daqianghuo-tang) has the anti-pathogenetic effects on the onset of collagen-induced arthritis in rats, by it`s inhibitory effects on the production of anti-collagen IgG. And also, Taeganghwal-tang(Daqianghuo-tang) has inhibitory effects on the progression of collagen-induced arthritis in rats, by it`s lowering effects on the secretion of TNF-α.

다탐색(多探索) 법을 통한 저자극성 액체 세정제 조성물 개발

김배환 ( Peter Kim ),현기안 ( Ki-an Hyeon ),정지윤 ( Ji-youn Chung ),윤삼숙 ( Sanm-sook Yoon ),강한철 ( Han Chyul Kang ),박선희 ( Sun Hee Park ),고강일 ( Kang Il Ko ),김기호 ( Ki Ho Kim ) 대한화장품학회 2005 대한화장품학회지 Vol.31 No.1

세정제에 널리 상용화되어 있는 알킬에톡시설페이트 계의 음이온 계면활성제는 피부 흡착의 특성 때문에 충분히 헹구어 내지 않으면 피부에 잔존되어 자극의 원인이 되어 염증 반응을 일으키게 된다. 따라서 기존의 음이온 계면활성제를 대체 또는 보완하기 위해 기존의 계면활성제들을 단백질 변성 실험, 세포 독성 그리고 IL-1α 측정을 통해 선별하였다. 본 연구는 저자극성의 음이온 또는 비이온, 양쪽성 이온의 14종의 계면활성제와 민감성 피부를 위해 제조된 13종의 기존 세정제 제품에 대한 세포독성을 실시하여, 가장 독성이 낮은 계면활성제로 sodium laureth sulfate (음이온), sodium cocoyl isethionate (음이온), sodium lauroamphoacetate (양성이온), cocamidopropyl betaine (양성이온), alkyl polyglycoside (비이온)가 선택되었고 2종의 기존 세정제 제품을 비교 제형으로 선택하였다. 5종의 계면활성제를 20종의 formulation으로 제조하여 단백질 변성(<3M SLS (13.2%)), 세포독성 실험 및 폐첩포 실험을 통하여 다시 5종을 선별하였다. 이들 제형을 진피 배양으로 세포독성 및 IL-1α 방춘량을 조사하여 가장 자극이 낮은 계면활성제 제형을 선택하였으며, 첨가된 계면활성제의 자극을 완화하기 위하여 항염과 보습 효과가 우수한 마치현 추출물(3%, 5%)과 fructan (3%, 5%)을 농도별로 첨가한 제형을 제조하여 가장 안전성이 뛰어난 농도를 선택하였다. 최종적으로 선택된 제형 5번을 3차원 세포 배양을 통한 인공피부를 이용하여 가장 자극이 낮게 나타난 기존의 제품들과 세포 독성 및 IL-1α 방출량을 비교 조사하여 저자극성의 액체 세정제를 개발하였다. Alkyl ethoxy sulfate type surfactants, widely used in commercial cleansers, are easily adsorbed to skin to often cause skin irritation and inflammation if not thoroughly rinsed nut. In order to replace or complement existing surfactants, we screened the existing surfactants through protein denaturation method, cell cytotoxicity assay and human IL-1α assay, etc. Fourteen surfactants have been chosen from among too irritant anionic, cationic and/or zwitter-ionic ones and investigated for cell cytotoxicity in human fibroblast cell lines using monolayer culture with the thirteen commercially available cleansers for sensitive skin. From these results, we selected 5 surfactants and 2 commercial cleansers (names not shown), such as sodium laureth sulfate (anionic), sodium cocoyl isethionate (anionic), sodium lauroamphoacetate (zwitter-ionic), and cocamidopropyl betaine (zwitter-ionic), alkyl polyglycoside (non-ionic). 20 formulations were made out of 5 surfactants and five of them were chosen through a protein denaturation method (lower than 3 M sodium dodecyl sulfate solution (13.2%)), cell cytotoxicity and human patch test. These five selected formulations containing preservatives were compared to two selected commercial cleansers by cell cytotoxicity and human IL-1α ELISA assay using dermal equivalent. Finally, we selected the best formulation. To this formulation, fructan (3% or 5%) or/and portulaca extract (3% or 5%) well known for its anti-inflammatory and moisturizing effects were added and investigated for cell cytotoxicity using dermal equivalent. In cytotoxicity assay using dermal equivalent, two formulations containing 5% fructan and 3% or 5% portulaca extract were less toxic than the others. In cytotoxicity assay and human IL-1α ELISA using 3D culture, the selected formulation containing 5% fructan and 5% portulaca extract showed better efficiency than those of the others and 2 commercial cleansers. As a result, we could develop a low irritant and safe liquid cleanser.

활락단(活絡丹)의 Adjuvant 유발 관절염 진행 억제 효과

김덕희 ( Deok Hee Kim ),정수현 ( Su Hyeon Jeong ),서일복 ( Il Bok Seo ),김순중 ( Soon Joong Kim ) 한방재활의학과학회 2011 한방재활의학과학회지 Vol.21 No.1

Objectives: This study was to investigate the antiarthritic effect of Hwallak-dan(Huoluo-dan) on the complete freund`s adjuvant(CFA)-induced arthritis in Lewis rats. Methods: Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups divided into normal(n=10), control(n=10) and treated(n=10) group. Animals of control group received normal saline for twenty days, treated group received extracts Hwallak-dan(Huoluo-dan) for same duration, light mineral oil only injected non-arthritic rats were served as normal group. The incidence of arthritis and arthritic index were observed after treatment. Body weight, paw edema volume and thickness of ankle joint were measured at 0, 11, 14, 17, 20 days after treatment. White blood cell(WBC) counts in blood were analysed at 20 days after treatment and tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 contents in paw exudate were analysed by ELISA at 20 days after treatment. Histopathology on the ankle joint were performed at 20 days after treatment. Results: 1. Incidence of arthritis of treated group was 60% and control group was 100% at 20 days after treatment. 2. Arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. 3. Paw edema volume and thickness of ankle joint of treated group was significantly decreased compared with control group at 20 days after treatment. 4. Total WBC of treated group was significantly decreased compared with control group at 20 days after treatment. 5. Neutrophils of treated group was significantly decreased compared with control group at 20 days after treatment. 6. TNF-α content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 7. IL-1β content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 8. IL-6 content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 9. Histopathological arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. Conclusions: These results indicate that Hwallak-dan(Huoluo-dan) has inhibitory effect on the development and progression of CFA-induced arthritis in rats.

가미소염탕(加味消炎湯)이 Monosodium Iodoacetate로 유발된 흰쥐의 골관절염에 미치는 영향

김용문 ( Yong Mun Kim ),정수현 ( Su Hyeon Jeong ),김순중 ( Soon Joong Kim ),서일복 ( Il Bok Seo ) 한방재활의학과학회 2008 한방재활의학과학회지 Vol.18 No.1

Objectives : This study was to investigate the effects of Gamisoyeoum-tang(Jiaweixiaoyan-tang) on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Monosodium iodoacetate induced arthritic rats were divided into control and treated group. Control group was taken distilled water for 20 days. Treated group was taken extracts of Gamisoyeoum-tang(Jiaweixiaoyan-tang) by orally for same duration. Normal group was injected with normal saline and was taken distilled water. Body weights were measured at 0, 5, 10, 15, 20 days after injection. At the end of experiment, gross and histopathological examination on the articular cartilages of the knee joints were performed. Contents of TNF-α, IL-1β, IL-6 in synovial fluids and proteoglycan contents of articular cartilages were analysed. COX-2 and iNOS immunohistochemical examination on the knee joints were performed. Results : 1. Body weights of the treated group were significantly increased compared with control group at 20 days after injection. 2. Grossly, the severity of osteoarthritis in the treated group were alleviated compared with control group. 3. PG contents in articular cartilages of the treated group were significantly increased compared with control group. 4. Histopathologically, degenerative and necrotic lesion of articular cartilages in the treated group were alleviated compared with those of the control group. 5. IL-1β contents in synovial fluids of the treated group were significantly decreased compared with control group. 6. Positive reactions of COX-2 in chondrocytes and synovial membranes of the treated group were decreased compared with the control group. Conclusions : On the basis of these results, we concluded that Gamisoyeoum-tang(Jiaweixiaoyan-tang) has anti-arthritic effects on the monosodium iodoacetate-induced osteoarthritis in rats. And it`s effects were related with reduced secretion of IL-1β and COX-2 from osteoarthritic chondrocytes and synovial membranes.

Immunostimulating Effects of Enzyme Hydrolysate of Ginseng Marc Polysaccharides in Immune-suppressed Mice

( Jeong Yeon Seo ),( Jun Il Kim ),( Seongcheol Kim ),( Gi Eun Park ),( Hyeon Jeong Kim ),( Jisun Lee ),( Jin Ree ),( Yong Il Park ) 한국키틴키토산학회 2018 한국키틴키토산학회지 Vol.23 No.2

Ginseng contains various health-beneficial bioactive compounds, such as ginsenosides and polysaccharides. Despite ginseng marc is produced after the extraction process and usually discarded as wastes, it still contains considerable amounts of potential bioactive compounds, including saponins and polysaccharides. Previously, we reported that glucan type ginseng oligosaccharides obtained by enzyme hydrolysis of ginseng marc-derived polysaccharides exhibit immunostimulatory activities in macrophages and, activated macrophages are in turn capable of inhibiting the growth of skin melanoma cells via induction of apoptosis. In the present study, an enzymatic hydrolysate (GEH) containing these ginseng oligosaccharides was prepared and immune-enhancing activities of GEH were evaluated in vivo using cyclophosphamide-treated immune-suppressed mice. Immunosuppression was induced by 3 day-intraperitoneal (i.p.) injection of cyclophosphamide in mice. When comparedh normal control group, the GEH administered orally for 29 days facilitated the recovery of weight gain, indices of spleen and thymus, and enhanced T lymphocyte and B lymphocyte proliferation, cytokine productions of IL-6, IL-4 and IL-10 in culture supernatants of Con A-treated splenic T lymphocytes, and increased the serum levels of IL-4 and IL-10 as well as NK cell activity. These results demonstrated that administration of GEH stimulates and enhances immune function in immune-suppressed mice. The results of this study suggest that GEH of ginseng marc can be developed as a health-beneficial food material with immunostimulatory activity.