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>

간내 담석과 동반된 간내 담도암에서의 p53과 Ki-ras의 발현

김명환,이성구,서동완,이승규,남승우,박능화,민영일,김연석,심기남,공경엽 대한소화기학회 1997 대한소화기학회지 Vol.30 No.5

Background/Aims: Hepatolithiasis or primary intrahepatic stones may be accompanied later by intrahepatic cholangiocarcinoma. This cancerous lesion is frequently associated with atypical hyperplastic epithelium that was suspected of being precancerous. To investigate the Ki-ras or p53 mutation may play a role in carcinogenesis, and to determine whether atypical hyperplastic epithelium may be precancerous, this study was performed in intrahepatic cholangiocarcinomas associated with hepatolithiasis. Methods: We examined 12 patients with intrahepatic cholangiocarcinomas associated with hepatolithiasis. Ki-ras point mutations were assessed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. The overexpression of p53 and point mutation of Ki-ras were examined in normal, hyperplastic, atypical hyperplastic, and can- cerous tissues separately. Results: The expressions of p53 protein were detected in 4 (33%) of 12 cholangiocarcinomas and Ki-ras point mutations at codon 12 were found in 2 (17%) of 12 cholangiocarcinomas. In those two carcinoma cases which contained the mutant sequence of Ki-ras, the same point mutation from wild type GGT (glycine) to GAT (aspartic acid) was. found in the associated atypical hyperplastic epithelium. However, none of the normal and hyperplastic epithelium harbored Ki-ras or p53 mutations. Conclusions: The overexpression of p53 may play a part in the carcinogenesis of some intrahepatic cholangiocarcinomas associated with hepatolithiasis, whereas the role of Ki-ras mutations in those cases is dubious. However, Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical hyperplastic epithelium associated with hepatolithiasis in certain cases, suggesting atypical hyperplastic epithelium may give rise to carcinoma.

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>

Activation of Transient Receptor Potential Melastatin Family Member 8 (TRPM8) Receptors Induces Proinflammatory Cytokine Expressions in Bronchial Epithelial Cells

김주희,Young Sook Jang,Hwan Il Kim,박지영,박성훈,Yong Il Hwang,Seung Hun Jang,Ki-Suck Jung,Hae Sim Park,Choon-Sik Park 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions: TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Interleukin-2와 결핵균 30 kDa 항원이 구개편도 및 말초혈액 T 세포 증식에 미치는 상승효과

박정규,박찬권,조은경,김화중,백태현,고필준,김병국,남부현,나기상,박찬일 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Widespread use of BCG has not controlled tuberculosis, and more effective vaccines are clearly needed. Although chemotherapy will remain the mainstay of antituberculosis treatment, the use of adjunctive immunotherapeutic modalitites is attractive, particularly in persons with drug-resistant tuberculosis. Administration of IL-2 or IFN-γto tuberculosis patients enhance bacillary elimination. Cell-mediated immunity is the critical protective immune response in tuberculosis. Mycobacterial antigens are recognized by T cells and that elicit production of protective cytokines are potentially important vaccine antigens. The 30 kDa antigen is secreted in large quantities by growing mycobacteria. That antigen elicits greater proliferation in lymphocytes from healthy tuberculin reactors than healthy tuberculin nonreactors. In this study, the T lymphocyte proliferative responses to 30 kDa antigen from Mycobactrium tuberculosis H37Rv were examined by using tonsilar and peripheral blood lymphocytes from PPD(+) and PPD(-) tonsilectomized persons. When cultured with 30 kD antigen, tonsilar mononuclear leukocytes and T cells of PPD(+) demonstrated more ^3H-thymidine incorporation than PPD(-) persons (stimulation index was 2.5 and 1.9, 0.8 and 1.0, repectively). Peripheral blood mononuclear cells (PBMC) and peripheral blood T lymphocytes were shown the similar responses to this antigen. The combination of IL-2 and 30 kDa antigen elicited a significant proliferative responsiveness in tonsilar mononuclear leukocytes and T cells of PPD(+) persons (SI was 20 and 14.1). PBMC and peripheral blood T cells of PPD(+) persons were also shown a significant responsiveness, but PPD(-) persons did not show. These results demonstrate that the 30 kDa antigen and IL-2 have a synergistic stimulatory property in mycobacteria sensitizing lymphocytes.

좌전하행지 관동맥 개구부위의 망사형의 관(Slotted Tube)스텐트와 나선형 코일(Coil)스텐트 삽입후 단기 및 장기 암상 경과의 비교

박훈기,박성욱,이일수,이상곤,김진우,이근,정상식,이철환,홍명기,김재중,박승정 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.6

Tobacco Smoking Could Accentuate Epithelial-Mesenchymal Transition and Th2-Type Response in Patients With Chronic Rhinosinusitis With Nasal Polyps

Lee Ki-Il,Han Younghwan,Ryu Jae-Sung,In Seung Min,Kim Jong-Yeup,Park Joong Su,Kim Jong-Seok,Kim Juhye,Youn Jubin,박석래 대한면역학회 2022 Immune Network Vol.22 No.4

Tobacco smoking (TS) has been known as one of the most potent risk factors for airway inflammatory diseases. However, there has been a paucity of information regarding the immunologic alteration mediated by TS in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To identify the effect of TS, we harvested human tissue samples (never smoker: n=41, current smoker: n=22, quitter: n=23) and analyzed the expression of epithelial-derived cytokines (EDCs) such as IL-25, IL-33, and thymic stromal lymphopoietin. The expressions of Th2 cytokines and total serum IgE showed a type-2 inflammatory alteration by TS. In addition, the epithelial marker E-cadherin and epithelial-mesenchymal transition (EMT)-associated markers (N-cadherin, α-SMA, and vimentin) were evaluated. Histological analysis showed that EDC expressions were upregulated in the current smoker group and downregulated in the quitter group. These expression patterns were consistent with mRNA and protein expression levels. We also found that the local Th2 cytokine expression and IgE class switching, as well as serum IgE levels, were elevated in the current smoker group and showed normal levels in the quitter group. Furthermore, the expressions of E-cadherin decreased while those of N-cadherin, α-SMA, and vimentin increased in the current smoker group compared those in the never smoker group. Taken together, these results indicate that TS contributes to the deterioration of pathogenesis by releasing local EDCs and Th2 cytokines, resulting in EMT in patients with CRSwNP. We verified that alterations of immunological response by TS in sinonasal epithelium can play a vital role in leading to CRSwNP.

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.

긴 관동맥병변에서 긴 스텐트삽입에 대한 임상경과 및 재협착율

김영학,박성욱,정상식,박훈기,이상곤,이일수,이철환,김재중,홍명기,박승정 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.6

The Korean Society of Gastroenterology & SIDDS 2040 : Slide Session ;K-LG-11 : Lower GI Tract ; Guggulsterone Ameliorates Colitis by Blocking Crosstalk Between Nf-κb and Trem-1

( Soo Jung Park ),( Ki Cheong Park ),( You Hyun Kang ),( Hyun A Jin ),( Xiu Mei Che ),( Seung Won Kim ),( Sung Pil Hong ),( Tae Il Kim ),( Won Ho Kim ),( Jae Hee Cheon ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Triggering receptor expressed on myeloid cells (TREM)-1 constitutively expressed in macrophage, and upregulated by bacterial components, such as lipopolysaccharide (LPS), and functions as an amplifying molecule in infi ammatory responses. Recent studies have reported that TREM-1 expression is up-regulated in patients with infi ammatory bowel disease (IBD). In this study, we expected that guggulsterone (GGS) functions as reducer of TREM-1 in macrophage and investigated the anti-infi ammatory effects of GGS via the inhibition of NF-κB/TREM-1 in mononuclear cells using RAW264.7 activated by LPS and TNBS-induced colitis model of knockout mice. Methods: We are checked the mRNA level of TREM-1 and toll like receptor 4 (TLR4) using real time RT-PCR and the protein level of IκBa and phospho-IκBa using western blotting and ELISA, and nuclear translocation of NF-κB using immunofi uorescence. MG132 and TREM-1 antibody were used to determine the interaction of NF-κ B and TREM-1 signaling. Mouse colitis is induced by the administration of TNBS into the colon. Results: GGS treatment decreased the mRNA and protein levels of TREM-1, TLR4, TNF-a, IL-6, IL17, COX-2, and MMP-9 by blocking the phosphorylation and degradation of IκBa as well as nuclear translocation of NF-κB in RAW264.7 macrophage activated by LPS. In the TNBS-induced colitis model, GGS reduced disease activity index (DAI), and infi ammation related protein expressions by suppressing NF-κB and TREM- 1 activation in colon mucosa. Conclusions: GGS blocks the NF-κB signaling pathway by targeting the TREM-1 in RAW264.7 macrophage activated by LPS and TNBS-induced mouse colitis model. Ourresults provide an insight into the mutual relationship NF-κB and TREM-1 signaling pathway. Eventually, these fi ndings shows that GGS has a anti-infi ammatory effects in macrophage cells through the regulation of the TREM-1 and NF-κB signaling, which suggests that GGS is a potential therapeutic agent for the treatment of IBD.