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>

Prevalence and Risk Factors of Atrophic Gastritis and Intestinal Metaplasia in a Korean Population Without Significant Gastroduodenal Disease

Kim, Nayoung,Park, Young Soo,Cho, Sung-Il,Lee, Hye Seung,Choe, Gheeyoung,Kim, In Wook,Won, Yoo-Deok,Park, Ji Hyun,Kim, Joo Sung,Jung, Hyun Chae,Song, In Sung Wiley (Blackwell Publishing) 2008 Helicobacter Vol.13 No.4

<P>BACKGROUND AND AIM: The prevalence of gastric cancer and Helicobacter pylori infection is unacceptably high in Korea. This study was performed to evaluate the prevalence of atrophic gastritis (AG) and intestinal metaplasia (IM) and to identify their risk factors with respect to H. pylori virulence factors, and environmental and host factors, in Korean population without significant gastroduodenal disease. METHODS: The study cohort consisted of 389 subjects (> or = 16 years). AG and IM were scored histologically using the Sydney classification in the antrum and body, respectively. Prevalences and bacterial factors (i.e. cagA, vacA m1, and oipA), environmental factors (i.e. smoking and alcohol), and host factors (i.e. genetic polymorphisms of IL-1B-511, IL-1RN, TNF-A-308, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, p53 codon 72, and ALDH2) were evaluated. RESULTS: Prevalences of AG in the antrum and body were 42.5% and 20.1%, and those of IM were 28.6% and 21.2%, respectively. The presences of AG and IM were significantly higher in H. pylori-positive than in the H. pylori-negative subjects. Multivariate analysis showed that the risk factors for AG were H. pylori infection, age > or = 61 years, and cagA and vacA m1 positivity. For IM the risk factors were H. pylori infection, age > or = 61 years, a smoking history (rather than current smoking), strong spicy food, occupation (unemployed or nonprofessional vs. professional), and the presence of IL10-592 C/A as opposed to A/A. In addition, IL6-572 G carrier was found to have a protective effect against IM development as compared with C/C. CONCLUSION: H. pylori infection was most important risk factor of AG and IM. Bacterial factors were found to be important risk factor for AG but environmental and host factors were more important for IM.</P>

부산·울산·경남지역 직업병 감시체계

김정일,김병권,김정원,채창호,이철호,강동묵,김지홍,김진하,김영욱,이영하,이지호,김정호,윤형렬,유철인,정백근,장태원,김운규,윤동영,강진욱,김종은,안진홍,이동준,장준호,이광영,송혜란,최영희,이용환,조병만,최홍렬,고상백,김은아,이유진,홍영습,정갑열,김정만,김준연 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

Objective: Occupational medicine specialists in the Busan, Ulsan and Kyung-Nam areas established an area-based occupational disease surveillance system and used this system to collected case information for the purpose of preventing occupational diseases Methods: l l hospital participated in this system. The authors selected five main diseases, which were hand-arm vibration syndrome (HAVS), work-related musculoskeletal disorder (WRMSD), occupational asthma, occupational skin disease and occupational and occupational lung cancer and established their case definitions. All cases were reported on the web, and real time analysis was conducted. Results: Between April 2001 and April 2003, 192 cases of HAVS, 118 cases of WRMSD, 33 cases of occupational asthma, 17 cases of occupational skin disease and 17 cases of occupational lung cancer (for a total of 377 cases of these five main diseases) were reported. most of the HAVS cases came from shipbuilding, and 172 of them (92.7%) were associated with grinding. Of the four main types of WRMSD, carpal tunnel syndrome (CTS) was the most prevalent with 46 cases and shipbuilding was also the main industry involved (83.9%). The ergonomic risk factors involved mainly associated with the hand. In 19 (57.6%) and 4 (12.1%) cases of occupational asthma, the agents involved. The causative agents of occupational lung cancer included Cr, welding fume, PAH, Ni, etc. 10(58.8%) of the cases were diagnosed as squamous cell carcinoma and 5(29.4%) as adenoma. Conclusion: This result showed that an area-based occupational disease surveillance system might provide an effective method of evaluating the prevalence of such diseases, however the Busan, Ulsan and Kyung-Nam provinces are too large to be treated as individual areas. Therefore, the authors suggest that each province should establish its own surveillance system.

IL-$1{\beta}$ 처리 백서 두개관 세포의 mineral trioxide aggregate에 대한 반응

이술현,박지일,김영준,Lee, Sool-Heon,Park, Ji-Il,Kim, Young-Joon 대한치주과학회 2009 Journal of Periodontal & Implant Science Vol.39 No.3

Purpose: The purpose of this study was to investigate the ability of Mineral trioxide aggregate(MTA) to support osteoclastic differentiation from fetal rat calvarial cell. Methods: In this study, response of IL-6, RANKL, and OPG in fetal rat calvarial cells stimulated with IL-$1{\beta}$ on MTA was evaluated by ELISA and RT-PCR. Results: The results were as follows; there was no significant difference between glass and MTA at 5days. In ELISA analysis, Glass group and MTA group showed similar IL-6 expression, Glass+IL-$1{\beta}$ group and MTA+IL-$1{\beta}$ group showed similar IL-6 expression. In RT-PCR analysis, Glass group and MTA group showed similar IL-6, RANKL, OPG mRNA expression, MTA+IL-$1{\beta}$ group and Glass+IL-$1{\beta}$ group showed 3 fold increase of IL-6 and RNAKL mRNA expression when compared with MTA group. All groups showed similar OPG mRNA expression. Conclusions: MTA does not suppress cell proliferation and increase the proinflammatory cytokine that induce osteoclastogenesis. Thus, MTA is biocompatible material that could be used in various clinical conditions.

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>

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.

Early Phase of UVB - induced GM - CSF Upregulation in Epithelial Cell Line is not Totally Dependent on IL - 1α

Park, Kyoung Chan,Kim, Kyu Han,Ahn, Jong Seong,Chung, Jin Ho,Youn, Jai Il,Whang, Ji Hwan,Youn, Sang Woong,Kim, Young Gull,Koh, Woo Seok,Jung, Hyun Chae 대한피부과학회 1997 Annals of Dermatology Vol.9 No.4

Backgrounds : It was demonstrated that ultraviolet(UV) B light induces the release of IL-la in cultured human epithelial cell line and augmentation of GM-CSF production by UVB is reported to be mediated by IL-1α in the murine keratinocyte cell line Pam 212. Objective : The purpose of this study was to evaluate the effects of UVB on kinetic profile of IL-1 and GM-CSF mRNA expression and to see whether synthesis of GM-CSF by UVB can be completely inhibited by blocking IL-1α mediated pathway. Method : We used a competitive RT-PCR for measuring cytokine gene expression in epithelial cell line after UV radiation. Results : The IL-1α mRNA increased as early as 1h after UV irradiation, and then decreased at 3h after the irradiation. Thereafter, the response of IL-1α mRNA was upregulated with a second peak at 6h after the UV irradiation. However, mRNA for GM-CSF increased at 1h after UV light exposure and anti-IL-1α antibodies could only partially inhibit UV-augmented GMCSF production. Conclusion : UVB induced GM-CSF production seemed to be mainly mediated by UVB induced IL-1α but these results suggest that UVB may also induce GM-CSF production through an IL-1α independent pathway.

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>

괴화 추출물이 대식세포에서의 nitric oxide와 interleukin-6의 생성에 미치는 영향

이지은,이주연,최점일,김종관,김성조,Lee, Ji-Eun,Lee, Ju-Youn,Choi, Jeom-Il,Kim, Chong-Kwan,Kim, Sung-Jo 대한치주과학회 2005 Journal of Periodontal & Implant Science Vol.35 No.1

Both nitric oxide (NO) and interleukin-6 (IL-6) have been thought to have a role in the pathogenesis of inflammatory periodontal disease as it does in other inflammatory diseases, and the inhibitors of NO and IL-6 production have been considered as potential anti-inflammatory agents. In this study, we evaluated methanol extract of Sophorae Flos for inhibition of NO and IL-6 production in Prevotella intermedia LPS-induced mouse macrophages RAW264.7 cells. Dried Sopharae Flos was sliced, and extracted with 100% methanol. LPS from p. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. NO production was assayed by measuring the accumulation of nitrite in culture supematants and IL-6 was measured using mouse IL-6 ELISA kit. Western blot analysis of iNOS and analysis of reverse transcription (RT)-PCR products were carried out. The methanol extract of Sophorae Flos concentration-dependently reduced the production of NO and the expression of iNOS protein and mRNA in RAw264.7 cells treated with P. intermedia LPS. Sophorae Flos also suppressed IL-6 production and the expression of IL-6 mRNA in RAw264.7 cells stimulated by P. intermedia LPS. The inhibition of NO and IL-6 production by Sophorae Flos may be useful in the therapy of inflammatory diseases such as periodontitis. This hypothesis, however, remains to be tested.

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>