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N-Acetyl-L-Cysteine에 의한 생쥐 골수유래 가지세포의 기능적 활성화 저해
정영주(Young-joo Jeong),맹형건(Hyung Gun Maeng),김민규(Min Kyu Kim),강재승(Jae Seung Kang),이왕재(Wang Jae Lee),황영일(Young-il Hwang) 대한해부학회 2008 Anatomy & Cell Biology Vol.41 No.2
N-acetyl-L-cysteine (NAC)은 thiol기를 포함하는 화합물로서, glutathione (GSH)의 전구체로 작용하여 포유류 세포 내에서 항산화제로 작용한다. 또한 항염기능이 있으며 호산구나 B세포, 가지세포 (dendritic cell, DC)와 같은 면역세포 들에 여러 가지 영향을 미치는 것으로 알려져 있다. 특히 가지세포에 작용하여 활성화를 억제하거나 가지세포에 의한 Th2 반응 유도에 관여한다고 알려져 있다. 그러나 이들 연구는 세부적인 사항에 있어서 그 결과가 서로 상치하는바가 많으며, 또한 조절T세포의 관점에서는 연구된 바가 없다. 따라서 본 연구에서는 NAC 처리가 가지세포 활성화에 미치는 영향을 재확인하였고, NAC 처리된 가지세포의 T세포 활성 능력 저하, 또는 Th2 반응 유도 여부를 알아보았다. 활성화 시 가지세포에서 증가하는 활성산소기 (reactive oxygen species)는 NAC 처리로 낮아져서, NAC이 가지세포에 항산화작용을 나타냄을 확인하였다. NAC 처리로 가지세포에서 보조자극인자인 CD40과 CD86의 발현이 저해되었으며, 활성화 시 정상적으로 낮아지는 포식기능은 처리된 NAC의 농도에 비례하게 보존되었다. 활성화 시 분비되는 IL-6, IL-10, IL-12는 모두 감소하였다. 이러한 NAC-DC와 함께 배양한 T세포의 증식이나 Th1 cytokine인 IFN-γ, Th2 cytokine인 IL-5의 분비가 모두 저하되어 Th1/Th2의 편중 없이 가지세포의 T세포 자극능력이 전반적으로 감소하였음을 나타내었다. 또한 T세포 배양액에서 IL-10과 TGF-β의 농도 역시 NAC-DC로 자극된 경우에 현저히 줄어서, NAC-DC에 의한 T세포 증식 감소 등은 조절T세포 유도에 의한 것이 아니라 T세포 무반응이 유도된 때문임을 나타내 주었다. N-acetyl-L-cysteine (NAC) is a thiol-containing compound and acts as a precursor for glutathione (GSH). It behaves as an antioxidant in mammalian cells and also exerts anti-inflammatory effects. NAC is also known to affect several immune cells including eosinophils, B cells, T cells, and dendritic cells (DC) in many aspects. Even though it has been reported that NAC inhibits DC activation and shifts the immune response to Th2, these studies exhibit some contradictory results in detail and do not give any information with respect to the induction of regulatory T cells. In this study, we re-analyzed the effects of NAC on DC during their activation. We also evaluated whether it induced T cell anergy, Th1/Th2 shift, or regulatory T cells. NAC suppressed the elevation of intracellular reactive oxygen species during DC activation. In parallel, it down-regulated surface expression of CD40 and CD86, suppressed the decrease of phagocytic function, lowered the secretion of cytokines such as IL-6, IL-10, and IL-12. All these effects showed dose-dependency. Thus, it seems likely that NAC inhibited DC activation with regard to their phenotype and cytokine secretion. When we evaluated the T cell-stimulating capacity of these NAC-DC, T cell proliferation and secretion of both Th1 (IFN-γ) and Th2 cytokine (IL-5) were decreased. This implies that the T cell-stimulating activity of NAC-DC decreased without any shift to Th1 or Th2 cytokine (IL-5). The secretion of IL-10 and TGF-β in the supernatants were also decreased, which suggests that the decrease of T cell proliferation and cytokine secretion is due to the induction of T cell anergy, rather than regulatory T cells.
Kang, Jae Seung,Kim, Ha Na,Jung, Da Jung,Kim, Jee Eun,Mun, Ga Hee,Kim, Yeong Seok,Cho, Daeho,Shin, Dong Hoon,Hwang, Young-Il,Lee, Wang Jae Williams & Wilkins 2007 The Journal of investigative dermatology Vol.127 No.3
It is well known that UVB (290–320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.Journal of Investigative Dermatology (2007) 127, 698–706. doi:10.1038/sj.jid.5700572; published online 28 September 2006
2,3-Dehydrosilybin Suppresses IL-31-Associated Pruritus Factors in Astrocytes and Microglia
Ji Hyeon Park,Jae Young Shin,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang,Byoung Ok Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
Chronic pruritus is the main symptom that increases the suffering of patients in hypersensitivity disorder disease. IL-31 is a pruritic cytokine with a primary objective to control itch. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. This study investigated the effect of DHS pretreatment on IL-31-associated pruritus in astrocytes and microglia. Pretreatment with DHS inhibited the production of IL-31 by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) stimulation in microglia. Pretreatment with DHS inhibited the phosphorylation of MAPK, STAT1 and NF-κB by LPS plus IFN-γ stimulation in microglia. In addition, DHS suppressed the expression of IL-31 receptor A in IL-31-treated astrocytes. DHS also inhibited lipocalin2 production in IL-31 stimulated astrocytes. Taken together, DHS has potential as a therapeutic agent for symptom relief by down-regulating the IL-31-mediated pruritus mechanism in microglia and astrocytes.
Jae Young Shin,Byoung Ok Cho,Ji Hyeon Park,Da Jeong Shin,Feng Wang,Suping Hao,Eun Seo Kang,Seon Il Jang 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Diospyros lotus (date plum) is a deciduous plant native to Asia including Korea and China. In traditional medicine, it has been used as an anticancer, antidiabetic, and antipyretic agent. Recently, the effect of Diospyros lotus on the improvement of sensitive skin was also reported. Chronic pruritus is one of the most difficult to manage symptoms of inflammatory skin disease. Recently, it was found that activation of STAT3 in astrocytes contributes to chronic pruritus. In this study, the effects of Diospyros lotus leaf extract (DLE) and its main component myricitrin on pruritus were investigated in in vitro and in vivo. Astrocytes were pretreated with DLE and myricitrin and stimulated with IL-6 to measure activation of STAT3 and production of lipocalin-2 (LCN2). We also investigated the effects of DLE and myricitrin on itch in chloroquine-induced itch mouse model. DLE and myricitrin blocked STAT3 activation and inhibited the release of LCN2 in astrocytes. Moreover, DLE and myricitrin inhibited the scratching behavior and inhibited the expression of glial fibrillary acidic protein (GFAP) in chloroquine-injected mice. Collectively, these studies suggest that modulation of DLE and myricitrin signaling pathways contribute to pruritus inhibition, thus suggesting potential for the prevention and/or treatment of pruritus caused by hypersensitivity skin conditions.
Lei Wang,Jae-Young Oh,Hye-Won Yang,Xiaoting Fu,Jae-Il Kim,You-Jin Jeon 제주대학교 해양과학연구소 2021 해양과환경연구소 연구논문집 Vol.45 No.-
The anti-inflammatory effect of a fucoidan with a molecular weight of 102.67 kDa isolated from an enzymatic digest of Sargassum fusiforme was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that the fucoidan significantly and dose-dependently inhibited the production of inflammatory molecules, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as improved the viability of LPS-stimulated RAW 264.7 cells. Moreover, the fucoidan suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by regulating the nuclear factor kappa B (NF-κB) pathway in LPS-stimulated RAW 264.7 cells. Furthermore, in vivo test results suggested that the fucoidan remarkably reduced reactive oxygen species (ROS), cell death, and NO levels in LPS-stimulated zebrafish in a dose-dependent manner. Taken together, these results demonstrated that the fucoidan isolated from S. fusiforme possesses strong anti-inflammatory activities in vitro and in vivo, and could prove as an important candidate to be used to develop anti-inflammatory agents in pharmaceutical and cosmeceutical industries.
Byoung Ok Cho,Jae Young Shin,Ji Hyeon Park,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Chronic pruritus is a symptom that reduces the quality of life of patients with inflammatory skin disease. Persistent activation of astrocytic signal transducer and activator of transcription 3 (STAT3) contributes to the elevation of chronic pruritus. STAT3 activation increases lipocalin-2 (LCN2) expression and enhances pruritus. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. In this study, the inhibitory effect of DHS on chronic pruritus was investigated in IL-6-treated astrocytes and chloroquine-injected mice. As a result, DHS prevented STAT3 activation and LCN2 production in IL-6-treated astrocytes. Moreover, DHS inhibited scratching and inhibited the expression of glial fibrillary acidic protein (GFAP) in chloroquine-injected mice. It also reduced the level of inflammatory cytokines in the mice serum. In conclusion, it was demonstrated that DHS suppressed itch through the STAT3 signaling pathway. Thus our results suggest that DHS can prevent and/or treat chronic itch.
( Hye Min Kim ),( Jae Seung Kang ),( Jong Pil Im ),( Se Yeon Bae ),( Ye Jin Kim ),( Hang Rae Kim ),( Joo Sung Kim ),( Young Il Hwang ),( Wang Jae Lee ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: Mucosal damage in inflammatory bowel diseases (IBDs) involves the dysfunctional immunoregulation of the gut. Among immunoregulatory factors, oxidative stress is abnormally high level in IBDs, and their destructive effects may contribute to the initiation or propagation of the disease. Vitamin C has both anti-oxidant and immunomodulatory effects. Methods: we investigated the effect of vitamin C on dextran sulfate sodium (DSS)-induced colitis in Gulo(-/-) mice which cannot synthesize vitamin C. Results: Vitamin C-insufficient Gulo(-/-) mice showed decreased survival with increased oxidative stress and more severe colitis. The production of interleukin (IL)-6 was higher, and STAT3 and Akt were more activated in DSS-treated vitamin C-insuffi cient Gulo(-/-) mice than in vitamin C-suffi cient Gulo(-/-) mice and wild-type mice. In contrast, the production of IL-22, the recruitment of NKp46(+) cells, and the activation of p38 MAPK were decreased in the vitamin C-insuffi cient Gulo(-/-) mice accompanied by decreased mucin-1 expression. Taken together, vitamin C insuffi ciency was associated with not only increased oxidative stress and IL-6 production but also decreased production of IL-22, which eventually induces severe colitis and death by DSS treatment. Conclusions: Therefore, our results suggest that vitamin C has a protective effect on DSS-induced colitis by regulating the production of cytokine and the induction of infl ammation.
Characterization of effector memory CD8+ T cells in the synovial fluid of rheumatoid arthritis.
Cho, Bon-A,Sim, Ji Hyun,Park, Ji Ah,Kim, Hye Won,Yoo, Wan-Hee,Lee, Seung-Hyun,Lee, Dong-Sup,Kang, Jae Seung,Hwang, Young-Il,Lee, Wang Jae,Kang, Insoo,Lee, Eun Bong,Kim, Hang-Rae Springer 2012 Journal of clinical immunology Vol.32 No.4
<P>Little is known about the cellular characteristics of CD8(+) T cells in rheumatoid arthritis (RA). We addressed this by investigating whether the frequency of the CD8(+) T cell subsets and their phenotypic characteristics are altered in the peripheral blood and synovial fluid (SF) from patients with RA. In this study, CD8(+) T cells, mainly CD45RA(-) effector memory (EM) CD8(+) T cells, were increased significantly in the SF, but not in the peripheral blood from RA patients, compared with healthy controls. The synovial EM CD8(+) T cells were activated phenotypes with high levels of CD80, CD86, and PD-1, and had a proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive cells were prone to apoptosis. In addition, EM CD8(+) T cells in the SF were less cytotoxic, as they expressed less perforin and granzyme B. In particular, the proportions of synovial fluid mononuclear cells that were CCR4(+)CD8(+) T cells and IL-4-producing CD8(+) T cells (i.e., Tc2 cells) were significantly higher than those in peripheral blood mononuclear cells of patients with RA and healthy controls. In addition, the number of IL-10-producing CD8(+) suppressor T (Ts) cells increased significantly in the SF of RA patients. Especially, CD8(+) T cells were inversely correlated with disease activity. These findings strongly suggest that EM CD8(+) T cells in the SF are increased, likely because of inflammation, and they may be involved in modulating inflammation, thereby affecting the development and progression of RA.</P>