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Original Articles
- IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction.
- Jae Joon Koh, Kyung Soo Ko, Jong Sang Park, Won Bae Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, San Goo Shin, Sung Wan Kim
- J Korean Endocr Soc. 2000;15(2):262-271. Published online January 1, 2001
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Abstract
PDF - BACKGROUND
Recently, we have reported that biodegradable poly [-(4-aminobutyl)-L-glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this study, we investigated whether the systemic administration of pCAGGS mouse IL-10 (mIL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. METHODS: PAGA/mIL-10 plasmid complexes were stable for more than 60 minutes, but the naked DNA was destroyed within 10 minutes by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3 week-old NOD mice. RESULTS: Serum mIL-10 level peaked at 5 days after injection, could be detected for more than 7 weeks. The prevalence of severe insulitis at 12 week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared to that of naked DNA injection (34.5%) and non-treated controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10 plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. CONCLUSION: The study presents the PAGA/DNA complex has the potential for the application of the prevention of autoimmune diabetes mellitus.
- The Regulation of OPG/OCIF mRNA Epression by IL-1beta in Peripheral Blood Mononuclear Cells.
- In Gul Moon, Ho Yeon Chung, Chang Sun Hwang, Young Soon Kang, Mi Sun Chung, Han Jin Oh, Kyu Hong Choi, Sun Woo Kim, Eui Hyun Kim, Youn Yee Kim, Chang Hoon Yim, Ki VOk Han, Hak Chul Jang, Hyun Koo Yoon, In Kwon Han
- J Korean Endocr Soc. 2000;15(2):204-213. Published online January 1, 2001
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Abstract
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- BACKGROUND
Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.
- Changes of Bone Mineral Density and Levels of Cytokines in the Culture Media of Bone Marrow Monocytes after Ovariectomy in Rats.
- Keun Yong Park
- J Korean Endocr Soc. 1997;12(2):215-221. Published online January 1, 2001
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Abstract
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- BACKGROUND
Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, IL-1 and TNF-a promote bone resorption by stimulating the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of these cytokines are mediated by estrogen. We performed this study to evaluate the effect of ovariectomy on bone mineral density and levels of cytokines in the culture media of bone marrow monocytes. METHODS: The experimental animals were 23 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 176.8 gm at the beginning of the study. Bilateral ovariectomy (n=13) and sham-operation (n=10) were performed in all rats from a ventral approach. Bone mineral density (BMD) of the total body and levels of IL-1 and TNF-a of culture media of bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH, FSH, E2 were measured by RIA assay. RESULTS: BMD of total body was lower after ovriectomy (0.24+-0.04g/cm) than before ovariectomy (0.27+-0.03g/cm), but there was no statistically significant difference in sham-operation group. Serum levels of LH, FSH were higher after ovariectorny (0.87+-0.36 mIU/mL, 9.47+-1.26 mIU/mL) than before ovariectomy (0.10+-0.06mIU/mL, 2.09+-0.41mIU/mL) (p<0.01) and serum level of E was lower after ovariectomy (10.98+-8.71pg/mL) than before ovariectomy (7350.77+-417.29 pg/mL) (p<0.01), respectively. Levels of IL-1 and TNF-a in culture media of bone marrow monocytes were higher after ovariectomy (23.48+-3.98pg/mL, 52.64+-5.31 pg/mL) than before ovariectomy (9.72+0.94pg/mL, 24.37+-3.39pg/mL) (p<0.01), but there were no statistically significant differences in the sharn-operation group. CONCLUSION: It is possible that increased production of IL-1 and TNF-a in estrogen deficiency induced by ovariectomy occures in the bone microenvironment and these cytokines may play a critical causal role in inducing bone loss.
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