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Park, Hun Hee,Kim, Myungshin,Lee, Bong-Hee,Lim, Jihyang,Kim, Yonggoo,Lee, Eun Jung,Min, Woo Sung,Kang, Chang Suk,Kim, Won Il,Shim, Sang In,Han, Kyungja Institute for Clinical Science] 2006 Annals of clinical and laboratory science Vol.36 No.1
<P>The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-gamma (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 +/- 1056) and lowest in the dysplastic AML group (960 +/- 545). The IFN-gamma level was highest in the acute promyelocytic leukemia (APL) group (495 +/- 159), and lowest in the ALL group (252 +/- 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 +/- 1049) and lowest in the APL group (397 +/- 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-gamma are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.</P>
Ryu, Chung Heon,Park, Sang-Hoon,Park, Soon A,Kim, Seong Muk,Lim, Jung Yeon,Jeong, Chang Hyun,Yoon, Wan-Soo,Oh, Won-il,Sung, Young Chul,Jeun, Sin-Soo Mary Ann Liebert 2011 Human gene therapy Vol.22 No.6
<P>Clinical trials of gene therapy using a viral delivery system for glioma have been limited. Recently, gene therapy using stem cells as the vehicles for delivery of therapeutic agents has emerged as a new treatment strategy for malignant brain tumors. In this study, we used human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) as delivery vehicles with glioma-targeting capabilities, and modified interleukin-12 (IL-12p40N220Q; IL-12M) as a novel therapeutic gene. We also engineered UCB-MSCs to secret IL-12M (UCB-MSC-IL12M) via tetrameric cell-permeable peptide (4HP4)-mediated adenoviral transduction. We confirmed the migratory capacity of UCB-MSC-IL12M toward GL26 mouse glioma cells by an in vitro migration assay and in vivo injection of UCB-MSC-IL12M into the ipsilateral hemisphere of implanted gliomas in C57BL/6 mice. In vivo efficacy experiments showed that intratumoral injection of UCB-MSC-IL12M significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with control mice. Antitumor effects were associated with increased local IL-12M levels, followed by interferon-γ secretion and T-cell infiltration in intracranial gliomas, as well as antiangiogenesis. Interestingly, tumor-free mice after UCB-MSC-IL12M treatment were resistant to ipsilateral and contralateral tumor rechallenge, which was closely associated with tumor-specific long-term T-cell immunity. Thus, our results provide the rationale for designing novel experimental protocols to induce long-term antitumor immunity against intracranial gliomas using UCB-MSCs as an effective delivery vehicle for therapeutic cytokines including IL-12M.</P>
Lee, Won-Jae,Hah, Young-Sool,Ock, Sun-A.,Lee, Jae-Hoon,Jeon, Ryong-Hoon,Park, Ji-Sung,Lee, Sang-Il,Rho, Na-Young,Rho, Gyu-Jin,Lee, Sung-Lim Elsevier 2015 Experimental cell research Vol.333 No.2
<P><B>Abstract</B></P> <P>The <I>in vitro</I> differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (<I>P</I><0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (<I>P</I><0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (<I>P</I><0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (<I>P</I><0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (<I>P</I><0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial <I>in vivo</I> immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. </LI> <LI> Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. </LI> <LI> SF-MSCs exhibited improved therapeutic effects than BM-MSCs. </LI> <LI> SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases. </LI> </UL> </P>
Woong-Il Kim,Je-Oh Lim,Se-jin Lee,So-Won Pak,In-Sik Shin,Jong-choon Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Silica dioxide nanoparticles (siONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinase (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP / MAPKs / AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, an this effect was closely related to the inhibition of TXNIP / MAPK/ AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.
TPA로 유도된 마우스 귀 부종 동물모델에서 소목추출물의 항염증 효과
음원식(Won Sik Eum),이광재(Kwang-Jae Lee),김대원(Dae Won Kim),임순성(Soon Sung Lim),강일준(Il-Jun Kang),박진서(Jinseu Park),최수영(Soo Young Choi) 한국식품영양과학회 2013 한국식품영양과학회지 Vol.42 No.3
본 연구를 통하여 TPA로 유도한 마우스 귀 부종 염증반응에 대한 소목추출물의 항염증 효능과 기전을 확인하였다. 소목추출물은 TPA로 유도한 마우스 귀 부종을 억제하였으며, TPA에 의한 염증관련 단백질인 COX-2 발현 및 cytokine(IL-6, TNF-α 그리고 IL-1β)의 mRNA 발현을 현저히 감소시켰다. 또한 TPA에 의한 NF-κB 및 MAPK의 활성을 억제하였다. 본 연구 결과, 소목추출물은 NF-κB 및 MAPK의 신호전달을 억제함으로서 항염증 효능을 나타내었다. This study investigated the anti-inflammatory effects of extracts from Caesalpinia sappan L. (CSL) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. Skin inflammation was detected by immunohistochemistry and the protein and mRNA expression levels of cyclooxygenase-2 (COX-2) and cytokines (IL-6, IL-1β and TNF-α) detected by Western blotting and RT-PCR. The activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) were analyzed by Western blotting. CSL extracts markedly inhibited the TPA-induced expression of COX-2 and pro-inflammatory cytokines. Also, CSL extracts significantly reduced the activation of NF-κB and MAPK. These results suggest that CSL extracts may serve as therapeutic agents against skin diseases related to inflammation.
Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3
Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.
Il Han Yoo,Won Gi Hong,Hunmin Kim,Byung Chan Lim,Hee Hwang,Jong Hee Chae,Ki Joong Kim,Yong Seung Hwang 대한의학유전학회 2013 대한의학유전학회지 Vol.10 No.2
Alexander disease is a rare degenerative leukodystrophy caused by dominant mutations in glial fibrillary acidic protein (GFAP). The neonatal form of Alexander disease may manifest as frequent and intractable seizures or obstructive hydrocephalus,with rapid progression leading to severe disability or death within two years. We report a case of a 50-day-old male who presented with intractable seizures and obstructive hydrocephalus. His initial magnetic resonance imaging (MRI) suggested a tumor-like lesion in the tectal area causing obstructive hydrocephalus. Despite endoscopic third ventriculostomy and multiple administrations of antiepileptic drugs, the patient experienced intractable seizures with rapid deterioration of his clinical status. After reviewing serial brain MRI scans, Alexander disease was suspected. Subsequently, we confirmed the de novo missense mutation in GFAP (c.1096T>C, Y366H). Although the onset was slightly delayed from the neonatal period (50 days old), we concluded that the overall clinical features were consistent with the neonatal form of Alexander disease. Furthermore, we also suspected that a Y366 residue might be closely linked to the neonatal form of Alexander disease based on a literature review.
Coupling of ent-Cyclic Peroxide and Ircinol A, Two Biologically Active Natural Marine Products
Lim, Chi-Won,Kim, Yeun-Kye,Jang, Mi-Soon,Park, Jin-Il,Park, Hee-Yeun The Korean Society of Fisheries and Aquatic Scienc 2006 Fisheries and Aquatic Sciences Vol.9 No.4
An acidic ent-cyclic peroxide was isolated from a sponge, Plakotis sp., and showed activity against leishmaniasis and pathogenic fungi. To improve the activity of this compound, we coupled the acidic ent-cyclic at the C1 position of ircinol A. Compound 3 exhibited significant activity against Leishmania mexican a and fungi with $IC_{50}$ values of 0.7 and $0.3-34{\mu}g/mL$, respectively. The yield of compound 3 was 98%.