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Jhun J.-Y.,Catholic Research Institute of Medical Science | Yoon B.-Y.,Inje University | Park M.-K.,Catholic Research Institute of Medical Science | Oh H.-J.,Catholic Research Institute of Medical Science | And 6 more authors.
Experimental and Molecular Medicine | Year: 2012

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-α. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA. © 2012 by the Korean Society for Biochemistry and Molecular Biology.


Kim J.H.,Catholic Research Institute of Medical Science | Kim I.-W.,Catholic Research Institute of Medical Science | Kim Y.-W.,Catholic Research Institute of Medical Science | Park D.C.,Catholic University of Korea | And 6 more authors.
Oncology Reports | Year: 2013

Cervical cancer is a serious disease that threatens the health of women worldwide. This study compared the sensitivities and false-positive rates of cervical cytology (Pap smear), human papilloma virus (HPV) DNA test, cervicography, first double-combined testing (cervical cytology and HPV DNA test), second double-combined testing (cervical cytology and cervicography) and triple-combined testing (cervical cytology, HPV DNA test and cervicography). The study included 261 patients screened for uterine cervical cancer. All women simultaneously underwent cervical cytology, HPV DNA test and cervicography for uterine cervical cancer screening and colposcopically directed biopsy for diagnostic evaluation. The triple-combined testing was consistently the most sensitive among the cervical screening tests. The second double-combined testing, with a sensitivity rate of 98.1% was more sensitive than the first double-combined test (92.3%). However, cervical cytology was most specific (93.5%) and showed the highest positive predictive value (77.8%). The sensitivity of cervical cytology was markedly improved in combination with HPV DNA test and cervicography. Thus, the triple-combined testing, which improves the high false negativity of cervical cytology, may be an effective tool in uterine cervical cancer screening, pending confirmation of the effectiveness in a mass screening study. © 2013 Spandidos Publications Ltd. All rights reserved.


Jung S.M.,Catholic University of Korea | Jung S.M.,Catholic Research Institute of Medical Science | Lee J.,Catholic Research Institute of Medical Science | Baek S.Y.,Catholic University of Korea | And 12 more authors.
Journal of Rheumatology | Year: 2015

Objective. To evaluate the expression of interleukin 33 (IL-33) and its receptor in sera and salivary tissues of patients with primary Sjögren syndrome (pSS), and to investigate the association with clinical profiles. Methods. Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined by ELISA and assessed for clinical correlation. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical staining and was further characterized by confocal microscopy. We also measured IL-33 production in salivary glandular epithelial cells by proinflammatory stimuli. Results. Serum levels of IL-33 and sST2 were higher in patients with pSS compared to those in controls (p = 0.018 and p < 0.0001, respectively). Among patients with pSS, sST2 concentration was associated with thrombocytopenia (p = 0.029) and correlated with disease duration (p = 0.013) and the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (p = 0.042). The expression of IL-33 and ST2 was elevated in salivary glands of patients with pSS with grade 2 inflammation, and diminished in advanced inflammation. In patients with pSS, IL-33 was mainly observed in epithelial and endothelial cells of glandular tissue. The production of IL-33 mRNA by salivary gland epithelial cell line increased under stimulation with interferon-γ. Conclusion. The expression of IL-33 and its receptor was elevated in sera and salivary tissues of patients with pSS. These results suggest that the IL-33/ST2 axis might have a role in the pathogenesis of pSS. Copyright © 2015. All rights reserved.


Park H.J.,Catholic University of Korea | Oh M.-K.,Catholic University of Korea | Kim N.-H.,Catholic University of Korea | Cho M.-L.,Catholic Research Institute of Medical Science | Kim I.-S.,Catholic University of Korea
Immunology | Year: 2013

Haptoglobin (Hp), a major acute-phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from patients with rheumatoid arthritis (RA). Specific Hp fragments of 28 000 and 15 000 molecular weight were identified in SF of patients with RA, and the two polypeptides were presumed to be fragments of the Hp β-chain (43 000 MW) produced by cleavage with plasmin. The 15 000 MW fragment, which is a C-terminal region of Hp, was observed at higher frequency and levels in RA than in osteoarthritis. Plasmin activity was also higher in SF of RA patients. A recombinant 15 000 MW Hp fragment up-regulated interlukin-6 expression in monocytic cells. These findings indicate that the C-terminal Hp fragment is generated by plasmin in local inflammatory environments and acts as an inflammatory mediator. They further suggest that a specific Hp fragment might be applied as a novel biomarker for the diagnosis and prognosis of inflammatory diseases such as RA. © 2013 John Wiley & Sons Ltd.

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