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1.
Thymic stromal lymphopoietin (TSLP) is a type II cytokine which is associated with most inflammatory allergic disorders in humans. It is produced mainly by epithelial cells with important role in the development of chronic inflammatory diseases by activating T-helper cell type-2 (TH2) pathways. In this study, a total of 16 peptides were prepared by solid phase peptide synthesis based on amino acid sequences of the interface between TSLP and TSLP receptor. Their TSLP inhibition activities were determined by ELISA assay. Among them, three peptides (6?8) exhibited >50% inhibition at concentration of 0.3 mM. They can be used as hit compounds for developing peptide-based TSLP inhibitors.  相似文献   
2.
In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.  相似文献   
3.
《Phytomedicine》2014,21(4):453-460
PurposeNaju Jjok (NJJ, Polygonum tinctorium) is a clear heat and release toxin medicinal. It has been used to treat various inflammatory diseases and as a dye in clothing in traditional Korean medicine. However, the effect of NJJ on atopic dermatitis (AD) has not been elucidated. Therefore, we examined whether NJJ would have an inhibitory effect on AD using the mimic AD murine model and in vitro model.MethodsWe treated NJJ on 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice, phorbol myristate acetate/calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells, and anti-CD3/anti-CD28-stimulated splenocytes. Histological analysis, ELISA, PCR, and Western blot analysis were performed.ResultsThe oral administration with NJJ suppressed the total clinical severity in DNFB-induced AD-like lesional skin. NJJ significantly suppressed the levels of inflammatory mRNA and protein in AD-like lesional skin. NJJ significantly suppressed the levels of IgE and interleukin-4 in the serum of DNFB-induced AD mice. The expression of mast cells-derived caspase-1 was suppressed by NJJ in AD-like lesional skin. In addition, topical application with NJJ improved clinical symptoms in DNFB-induced AD mice. The topical application with NJJ significantly suppressed the levels of IgE and histamine in the serum of DNFB-induced AD mice. NJJ suppressed the production and mRNA expression of TSLP by blockade of caspase-1 signal pathway in the activated HMC-1 cells. Furthermore, NJJ significantly decreased the production of tumor necrosis factor-α from the stimulated splenocytes.ConclusionsIn conclusion, these results propose curative potential of natural dye, NJJ by showing the scientific evidence on anti-AD effect of NJJ which has been used traditionally.  相似文献   
4.
Moon PD  Kim HM 《Cytokine》2011,54(3):239-243
Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease. Although there are many reports regarding function and regulatory mechanism of TSLP in dendritic cells and/or T cells, the regulatory mechanism of TSLP in mast cells has not been fully elucidated. Here, we describe how TSLP is expressed and produced by inflammatory stimulus in mast cells. TSLP mRNA was expressed by phorbol myristate acetate (PMA) plus A23187 stimulation in HMC-1 cells and reached its peak 5h after PMA plus A23187 stimulation. The expression of TSLP mRNA was inhibited by nuclear factor (NF)-κB inhibitor. In addition, NF-κB luciferase activity was inhibited by caspase-1 inhibitor, indicating that caspase-1 is an upstream of NF-κB in mast cells. Furthermore, caspase-1 inhibitor decreased the expression of TSLP mRNA induced by PMA plus A23187. Finally, TSLP production was inhibited by both caspase-1 inhibitor and NF-κB inhibitor. These results provide proof of principle that TSLP can be expressed and produced through caspase-1 and NF-κB in mast cells and open new perspectives to pharmacologically manipulate the expression and production of TSLP by molecules acting on the caspase-1 and NF-κB pathway.  相似文献   
5.
Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell-mediated Th2-type inflammatory responses and is considered as a master switch for allergic inflammation. In this study, we found increased levels of TSLP and, also TNF-alpha as previously reported, in synovial fluid specimens derived from patients with rheumatoid arthritis (RA) when compared with those from patients with osteoarthritis (OA). In addition, TNF-alpha up-regulated TSLP expression in RA- and OA-derived synovial fibroblasts, which was inhibited by IFN-gamma. Furthermore, anti-TSLP neutralizing antibody ameliorated a TNF-alpha-dependent experimental arthritis induced by anti-type II collagen antibody in mice. Collectively, these results suggest that TSLP, as a downstream molecule of TNF-alpha, may be involved in the pathophysiology of inflammatory arthritis. TSLP might thus play a role not only in allergic diseases but also in inflammatory arthritis such as RA.  相似文献   
6.
Thymic stromal lymphopoietin (TSLP) endows human blood‐derived CD11c+ dendritic cells (DCs) and Langerhans cells (LCs) obtained from human epidermis with the capacity to induce pro‐allergic T cells. In this study, we investigated the effect of TSLP on umbilical cord blood CD34+‐derived LC‐like cells. These cells are often used as model cells for LCs obtained from epidermis. Under the influence of TSLP, both cell types differed in several ways. As defined by CD83, CD80 and CD86, TSLP did not increase maturation of LC‐like cells when compared with freshly isolated LCs and epidermal émigrés. Differences were also found in the production of chemokine (C‐C motif) ligand (CCL)17. LCs made this chemokine only when primed by TSLP and further stimulated by CD40 ligation. In contrast, LC‐like cells released CCL17 in response to CD40 ligation, irrespective of a prior treatment with TSLP. Moreover, the CCL17 levels secreted by LC‐like cells were at least five times higher than those from migratory LCs. After maturation with a cytokine cocktail consisting of tumour necrosis factor‐α, interleukin (IL)‐1β, IL‐6 and prostaglandin (PG)E2 LC‐like cells released IL‐12p70 in response to CD40 ligation. Most importantly and in contrast to LC, TSLP‐treated LC‐like cells did not induce a pro‐allergic cytokine pattern in helper T cells. Due to their different cytokine secretion and the different cytokine production they induce in naïve T cells, we conclude that one has to be cautious to take LC‐like cells as a paradigm for ‘real’ LCs from the epidermis.  相似文献   
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8.
摘要 目的:观察牙周-正畸联合治疗对侵袭性牙周炎(AgP)患者牙周功能和龈沟液胸腺基质淋巴细胞生成素(TSLP)、白介素-33(IL-33)的影响,并分析其预后的影响因素。方法:选择2017年1月至2021年6月期间我院收治的AgP患者119例,根据治疗方式的不同分为对照组(牙周基础治疗)和联合组(牙周-正畸联合治疗),例数分别为58例和61例。对比两组患者的牙周功能[牙周袋深度(PD)、牙龈指数(GI)、菌斑指数(PLI)、临床附着丧失(AL)]和龈沟液TSLP、IL-33水平,根据PD判断联合组患者的预后情况,采用单因素、多因素Logistic回归分析预后的影响因素。结果:两组治疗后PD、GI、PLI、AL均较治疗前下降,且联合组低于对照组(P<0.05)。两组治疗后龈沟液TSLP、IL-33水平均较治疗前下降,且联合组低于对照组(P<0.05)。61例采用牙周-正畸联合治疗的AgP患者,6个月后复查发现,PD<4 mm的患者有38例(预后良好组),PD≥4 mm患者有23例(预后不良组)。单因素分析结果显示,牙周-正畸联合治疗AgP患者的预后与患牙上下/前后分布位置、患牙最深PD值、牙槽骨高度基线值、PLI、根型态异常情况有关(P<0.05)。多因素Logistic回归分析结果显示:患牙分布位置为下颌牙、根型态存在异常情况、患牙分布位置为前牙、患牙最深PD值偏大、PLI偏高、牙槽骨高度基线值偏高均是牙周-正畸联合治疗AgP患者不良预后的危险因素(P<0.05)。结论:与单纯的牙周基础治疗相比,牙周-正畸联合治疗可有效改善AgP患者的临床症状,控制局部炎性反应。同时,患牙上下/前后分布位置、患牙最深PD值、牙槽骨高度基线值、PLI、根型态异常情况均是牙周-正畸联合治疗AgP患者预后的影响因素,需引起临床重视。  相似文献   
9.
《Cell reports》2023,42(2):112073
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10.
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