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Wee, Yu-Mee,Lim, Dong-Gyun,Kim, Yang-Hee,Kim, Jin-Hee,Kim, Song-Cheol,Yu, Eunsil,Park, Myung-Ok,Choi, Monica Young,Park, Youn-Hee,Jang, Hyuk-Jai,Cho, Eun-Young,Cho, Myung-Hwan,Han, Duck-Jong SAGE Publications 2008 CELL TRANSPLANTATION Vol.17 No.10
<P>The necessity to transplant islet tissue without the need for immunosuppressant therapy has led to the development of materials for immune modulation. Pegylation makes islets antigenically silent, protecting them from the adsorption of foreign protein and thus avoiding immune injury. The aim of this study is to determine whether pegylation of islets prolongs islet survival and function both during tissue culture and posttransplantation. We used cyanuric chloride-activated methoxy-polyethylene glycol for cell surface modification. To detect the pegylation effect on splenocytes, we measured antibody binding inhibition and abrogation of lymphocyte proliferation. To detect the pegylation effect on islet grafts, we performed rodent islet transplantation. Islet viability and function were maintained after pegylation. Pegylated islets showed a 90% decrease in antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte culture. However, when pegylated islets were transplanted, no prolongation of graft survival was observed. When a subtherapeutic dose of immunosuppressant was given at the time of transplantation of pegylated islets, islet graft survival was significantly prolonged. In addition, when rats were sensitized with donor splenocytes, graft survival was prolonged by pegylation. We observed that pegylation of islets, combined with a subtherapeutic dose of immunosuppressant, protects the graft from rejection. Prolonged graft survival in sensitized recipients showed that pegylation of islets shifted the pattern of rejection from an acute humoral response to a less aggressive cellular alloresponse.</P>
( Yu Mee Wee ),( Heounjeong Go ),( Monica Young Choi ),( Hey Rim Jung ),( Yong Mee Cho ),( Young Hoon Kim ),( Duck Jong Han ),( Sung Shin ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.9
Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal NKp46<sup>+</sup>DX5<sup>+</sup> NK cells, renal NKp46<sup>+</sup>DX5<sup>-</sup> cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model. [BMB Reports 2019; 52(9): 554-559]
Wee, Yu-Mee,Jung, Joo-Hee,Kim, Yang-Hee,Choi, Monica-Y,Kim, Young-Hoon,Choi, Do-Sook,Cho, Myung-Hwan,Han, Duck-Jong SAGE Publications 2016 Experimental biology and medicine Vol.241 No.11
<P>The goal of this study was to identify immunological markers for use in antigen-specific assays that predict long-term survival after renal allograft and distinguish stable-functioning (SP) patients from poorly functioning (PP) patients. For this prospective study, 20 patients were enrolled. Eight SP and six PP patients were enrolled in this study. Serum cytokine/chemokine levels were analyzed by the Luminex multiplex assay. To detect indirect alloreactive T cells, we performed indirect mixed lymphocyte reaction using donor-antigen-pulsed autologous dendritic cells as stimulators. Serum induced protein-10 levels were significantly higher in the serum of PP patients, whereas sCD40L levels were higher in SP patients. The PP patients had significantly higher numbers of donor-specific CD4(+)CD43(high)CD45RO(+) T cells after indirect allostimulation, whereas this cell population was unchanged in SP patients. The donor-specific CD4(+)CD43(high)CD(45)RO(+) T cells had the effector memory T cell phenotype. Prospectively, we studied whether these cells influence graft outcome and found that their strong proliferation in pre-transplant patients is related to a poorly functioning graft. Indirectly allostimulated CD4(+)CD43(high)CD45RO(+) T cells may not only contribute to chronic allograft nephropathy development but may also have a role in the progression of acute rejection. Thus, these cells may have potential use as immune-monitoring markers in a noninvasive in vitro assay that predicts graft outcome.</P>
Yu-Mee Wee,Hae-Won Lee,Monica Young Choi,Hey Rim Jung,Ji Yoon Choi,Hyun Wook Kwon,Joo Hee Jung,Young Hoon Kim,Duck Jong Han,Sung Shin 한국간담췌외과학회 2018 Annals of hepato-biliary-pancreatic surgery Vol.22 No.4
Backgrounds/Aims: Compared with a single urinary biomarker, a composite of multiple urinary biomarkers may be more helpful for differentiating tubulointerstitial inflammation from interstitial fibrosis/tubular atrophy (IFTA) in kidney allografts. Methods: In this cross-sectional cohort study, we collected urine samples from 115 patients with for-cause biopsy, 53 patients with stable allografts, and 50 living kidney donors. We measured the urinary levels of transglutaminase 2 (TG2), syndecan-4 (SDC4), alpha 1 microglobulin (A1M), interferon-inducible protein 10 (IP-10), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Results: The for-cause biopsy group showed significantly higher levels of log<SUB>e</SUB>TG2/Cr, log<SUB>e</SUB>A1M/Cr, log<SUB>e</SUB>IL-6/Cr, and log<SUB>e</SUB>MCP-1/Cr compared with other groups. In the for-cause biopsy group, log<SUB>e</SUB>TG2/Cr level was positively correlated with the severity of IFTA. After adjusting for age, sex, body mass index, diabetes, hypertension, cardiovascular disease, and the interval between kidney transplant and biopsy, TG2 and the interval between transplant and biopsy were significantly correlated variables for the severity of IFTA. Regarding tubulointerstitial inflammation, Body mass index, TG2, SDC4, and IP-10 were positively-correlated variables, and MCP-1 and the interval between transplant and biopsy were negatively-correlated variables. Conclusions: Our results show that post-transplant urinary levels of TG2, SDC4, MCP-1 and IP-10 may be a useful biomarker for tubulointerstitial inflammation and IFTA.
Kim, Yu Jeong,Lee, Hyun Ju,Ryu, Jin Suk,Kim, Yun Hee,Jeon, Saewha,Oh, Joo Youn,Choung, Ho Kyung,Khwarg, Sang In,Wee, Won Ryang,Kim, Mee Kum Masson Pub. USA 2018 Cornea Vol.37 No.1
PURPOSE:: To investigate the efficacy and safety of transplantation with biomaterial-free cultured oral mucosal epithelial cell sheets (COMECs) for ocular reconstruction in subjects with total limbal stem cell deficiency. METHODS:: A prospective clinical trial (NCT02149732) was conducted in 8 subjects with total limbal stem cell deficiency after approval from the institutional review board of Seoul National University Hospital (H-0707-043-213) and the Ministry of Food and Drug Safety of Korea. COMECs were prepared in a culture system without the use of any temperature-sensitive polymers or carriers. The COMECs were transplanted without suture fixation. Four subjects underwent penetrating keratoplasty after stabilization of the COMEC transplant. Stable epithelialization, changes in visual acuity, and postoperative complications were evaluated for 6 months. Corneal cytokeratins (K) of 4 subjects who underwent penetrating keratoplasty were stained with an immunofluorescent agent. RESULTS:: The ocular surface was successfully reconstructed in 6 eyes. Complete stable epithelialization was achieved within a mean of 53.6 days. Visual improvement (≥2 lines) was achieved in 62.5% of the eyes. K12 (corneal phenotype), K4, and K13 (mucosal phenotype) were well expressed in grafts after keratoplasty, whereas K1, K8, and K19 were barely expressed. No ocular infections, local tumor formation, or remarkable systemic complications were observed. Ocular reconstruction using COMECs failed in 2 eyes, which had full symblepharon in 4 quadrants. CONCLUSIONS:: Transplanting biomaterial-free COMECs seems to be an efficient and safe procedure to reconstruct the ocular surface in patients who are completely limbal stem cell deficient without a full symblepharon.
Comparison of Topical Application of TSG-6, Cyclosporine, and Prednisolone for Treating Dry Eye
Kim, Yu Jeong,Ryu, Jin Suk,Park, Se Yeon,Lee, Hyun Ju,Ko, Jung Hwa,Kim, Mee Kum,Wee, Won Ryang,Oh, Joo Youn Masson Pub. USA 2016 Cornea Vol.35 No.4
<P>Purpose: To compare the therapeutic effects of topical tumor necrosis factor (TNF)-alpha-stimulated gene/protein-6 (TSG-6) with those of cyclosporine and prednisolone eye drops in NOD.B10.H2(b) mice, a model for inflammation-mediated dry eye. Methods: The 12-week-old NOD.B10.H2(b) mice were topically administered recombinant TSG-6 (0.1%) 4 times a day, 0.05% cyclosporine (Restasis) twice a day, or 1% prednisolone (Pred Forte) 4 times a day for 1 week. Aqueous tear production was measured by phenol red thread test, and corneal epithelial damage was observed with lissamine green and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Conjunctival goblet cell number was evaluated with periodic acid-Schiff staining. The levels of inflammatory cytokines were analyzed in the ocular surface (cornea and conjunctiva) and intraorbital gland. The dose-dependent effects of topical TSG-6 (0.001, 0.01, and 0.1%) were tested. Results: Tear production and goblet cell density were significantly increased in all groups receiving TSG-6, cyclosporine, and prednisolone. Corneal epithelial staining was markedly reduced by TSG-6 and cyclosporine but not by prednisolone. In prednisolone-treated eyes, corneal epithelial thickness was decreased, and apoptosis of corneal epithelial cells was increased. The levels of interferon gamma and TNF-alpha in the ocular surface and intraorbital gland were significantly repressed by TSG-6 and cyclosporine, and prednisolone treatment significantly reduced the level of interferon gamma. The effects of TSG-6 on the ocular surface and tear production were dose dependent. Conclusions: Topical TSG-6 was as effective in inflammation-mediated dry eye as cyclosporine eye drops. Topical prednisolone suppressed inflammation but induced apoptosis in the corneal epithelium.</P>
Oh, Hyun-Mee,Lee, SungGa,Na, Bo-Ra,Wee, Hyun,Kim, Sang-Hyun,Choi, Suck-Chei,Lee, Kang-Min,Jun, Chang-Duk,Wang, Yu-li American Society for Cell Biology 2007 Molecular biology of the cell Vol.18 No.6
<P>No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids (<SUP>507</SUP>RKIKK<SUP>511</SUP>) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the<SUP>507</SUP>RKIKK<SUP>511</SUP>significantly delayed the LFA-1-dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that<SUP>507</SUP>RKIKK<SUP>511</SUP>is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.</P>
Jee Yeon Kim,Yu-Mee Wee,Monica Young Choi,Hey Rim Jung,Ji Yoon Choi,Hyun Wook Kwon,Joo Hee Jung,Yong Mee Cho,Heounjeong Go,Minkyu Han,Young Hoon Kim,Duck Jong Han,Sung Shin 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.97 No.1
Purpose: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. Methods: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. Results: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. Conclusion: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.