• IMMUNE NETWORK
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• 제22권5호
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• pp.40.1-40.24
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• 2022

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.

• International Journal of Stem Cells
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• 제16권2호
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• 한국토양비료학회지
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• 제45권5호
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• pp.704-710
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• 2012

경사지 배수불량 논에서 밭작물의 안정적인 재배를 위한 배수개선 방법을 개발하기 위하여 논둑아래 기저부에 1열로 명거 (겉도랑 배수), 비닐차단막, 암거 (속도랑 배수), 관다발 등 네 가지 종류의 배수시설을 설치하여 배수개선 방법에 따른 토양의 물리적 특성변화를 비교 분석한 결과 다음과 같은 결론을 얻었다. 배수방법별 토양의 용적밀도는 배수방법 간에 큰 차이가 없었으나 집적층 (B층)의 투수력은 암거배수구가 $2.67cm\;hr^{-1}$로 가장 높았고 다음은 관다발배수 $1.53cm\;hr^{-1}$이었으며, 명거배수, 비닐차단막은 $0.8cm\;hr^{-1}$내외로 낮은 경향을 보였다. 경작층 (Ap)의 액상은 명거배수, 비닐차단막 처리구가 35% 내외로 높은 경향을 보였으나 암거배수구에서는 수분함량이 크게 감소되었다. 또한 암거배수구의 기상은 32 ~ 35% 내외로 명거배수, 비닐차단막, 관다발 처리구 17 ~ 20% 보다 상대적으로 높아 공극률이 증가하는 것으로 나타났다. 명거배수 처리구의 토색은 수분과다와 높은 지하수위로 환원작용이 일어나 회색을 보인 반면 암거배수구에서는 투수성 및 통기성이 증가하여 회색층의 토색이 명갈색을 변화되었고 환원층의 출현 깊이가 깊어지고 점차 층위분화가 진행됨을 확인할 수 있었다. 강우 후 토양 깊이별 수분함량 변화를 분석한 결과 명거배수 처리구의 표토에서는 7일이 경과하여야 토양수분이 30 mm이하로 감소되었으나 20 cm 이하의 깊이에서는 항상 수분이 과잉된 상태로 지속되는 경향을 보였다. 반면 암거 배수 처리구에서는 강우 후 5 일이 경과 후에 토양 30 cm 깊이까지 수분함량이 30 mm 이하로 감소되어 배수개선 효과가 가장 높았다. 따라서 "배수불량"인 경사지 논에서 논둑 밑 1열의 암거배수 시설 설치가 명거배수, 비닐차단막, 관다발 배수방법에 비해 토양의 물리성 개선효과가 높아 밭작물의 안정적인 생산과 농지자원의 이용전환 즉 논을 밭으로 이용해야 하는 범용농지 기반 조성을 위한 저비용의 실용적인 배수개선 방법으로 이용성이 높은 것으로 판단되었다.