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Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population
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作者 Siyu Hao Yu Zhang +4 位作者 Anqi Yin Ying Lyu Nannan Tong Jiangtian Tian Yuzhen Li 《Frigid Zone Medicine》 2024年第2期96-101,共6页
Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling... Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China. 展开更多
关键词 toll-like receptors 2 PSORIASIS POLYMORPHISM SUSCEPTIBILITY
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Relationship of Toll-Like Receptors 2 and 4 Gene Polymorphisms with Essential Hypertension in Chinese Han Population
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作者 Huabei Wu Shijie Yin 《Journal of Biosciences and Medicines》 CAS 2023年第2期53-63,共11页
Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In thi... Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In this study, we evaluated the association in a sample of members of the Chinese Han population. Method: We selected four single nucleotide polymor-phisms (SNP) of TLR2 (rs3804099, rs3804100, rs7656411) and TLR4 (rs1927906) genes, and measured the distributions of genotypic and allelic frequencies in 1063 participants, including 391 essential hypertension pa-tients and 672 controls. Result: No significant differences in the genotypic and allelic frequencies of the four SNPs were detected between cases and controls. However, three haplotypes, CCG, TTG and TTT of TLR2, were significantly associated with a decrease in the risk of essential hyperten-sion (OR: 0.512, 95% CI: 0.397 - 0.660, P P = 0.0038;OR: 0.797, 95% CI: 0.667 - 0.952, P = 0.0122, respectively). Inversely, the risk of essential hypertension increased sig-nificantly in patients with the CTG, TCG or TCT haplotypes (OR: 2.924, 95% CI: 2.157 - 3.963, P P P Conclusion: Our study suggested that haplotypes (CCG, TTG, TTT, CTG, TCG and TCT) of TLR2 might have profound effects on the development of essential hypertension in the Chinese Han population. 展开更多
关键词 toll-like receptor 2 toll-like receptor 4 Single-Nucleotide Polymor-phisms Essential Hypertension INFLAMMATION
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人Toll-like receptor 2胞外段的克隆和表达 被引量:4
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作者 刘艳君 朱平 +1 位作者 韩强涛 富宁 《免疫学杂志》 CAS CSCD 北大核心 2003年第5期332-335,共4页
目的 克隆、表达人Toll-like receptor2(TLR2)胞外段(A26-T588)基因,获得人TLR2胞外段蛋白。方法 RT-PCR扩增TLR2胞外段基因,以pcDNA3.1+质粒为载体在HEK293细胞中表达TLR2胞外段蛋白,同时以pcDNA3.1+/TLR2(A26-T588)重组质粒免疫昆明鼠... 目的 克隆、表达人Toll-like receptor2(TLR2)胞外段(A26-T588)基因,获得人TLR2胞外段蛋白。方法 RT-PCR扩增TLR2胞外段基因,以pcDNA3.1+质粒为载体在HEK293细胞中表达TLR2胞外段蛋白,同时以pcDNA3.1+/TLR2(A26-T588)重组质粒免疫昆明鼠,制备抗TLR2胞外段蛋白多抗。结果 PCR扩增及重组质粒测序结果表明成功地构建了pcDNA3.1+/TLR2(A26-T588)真核表达质粒,SDS-PAGE分析纯化产物在M_r为68000处出现明显蛋白条带。重组质粒DNA免疫小鼠3次后,血清抗体滴度可达1∶250。TLR2胞外段蛋白可与LPS结合,并在一定的质量浓度范围内呈剂量依赖性。结论 构建的pcDNA3.1+/TLR2(A26-T588)真核表达质粒可在哺乳动物细胞中表达TLR2胞外段蛋白,并与重组质粒DNA免疫小鼠抗血清及TLR2单克隆抗体TL2.1特异性反应,由此证明其表达正确。 展开更多
关键词 toll-like receptor 2 胞外段蛋白 多克隆抗体
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广谱模式识别分子Toll-like receptor 2的研究进展 被引量:11
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作者 刘艳君 富宁 《免疫学杂志》 CAS CSCD 北大核心 2002年第3期234-236,共3页
TLR-2(Toll-like receptor 2,TLR-2)是哺乳动物TLRs(Toll-like receptors,TLRs)家族的一员,作为细胞表面的天然受体蛋白,主要参与病原微生物产物的识别及炎症信号传导,介导天然抗感染兔疫;最近又发现其参与机体对非感染因子所致炎... TLR-2(Toll-like receptor 2,TLR-2)是哺乳动物TLRs(Toll-like receptors,TLRs)家族的一员,作为细胞表面的天然受体蛋白,主要参与病原微生物产物的识别及炎症信号传导,介导天然抗感染兔疫;最近又发现其参与机体对非感染因子所致炎性组织损伤的识别。通过对TLR-2参与的识别和细胞内信号传导机制的研究,可为深入探讨抵御微生物感染的机制、对自身正常与非正常组织的识别提供新的思路。 展开更多
关键词 toll-like receptor2 天然免疫 TLR-2 广谱模式识别
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Argon preconditioning protects neuronal cells with a Toll-like receptor-mediated effect 被引量:3
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作者 Stefanie Scheid Adrien Lejarre +3 位作者 Jakob Wollborn Hartmut Buerkle Ulrich Goebel Felix Ulbrich 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第6期1371-1377,共7页
The noble gas argon has the potential to protect neuronal cells from cell death.So far,this effect has been studied in treatment after acute damage.Preconditioning using argon has not yet been investigated.In this stu... The noble gas argon has the potential to protect neuronal cells from cell death.So far,this effect has been studied in treatment after acute damage.Preconditioning using argon has not yet been investigated.In this study,human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon(25%,50%,and 74%;21%O_(2),5%CO_(2),balance nitrogen)at different time intervals before inflicting damage with rotenone(20μM,4 hours).Apoptosis was determined by flow cytometry after annexin V and propidium iodide staining.Surface expressions of Toll-like receptors 2 and 4 were also examined.Cells were also processed for analysis by western blot and qPCR to determine the expression of apoptotic and inflammatory proteins,such as extracellular-signal regulated kinase(ERK1/2),nuclear transcription factor-κB(NF-κB),protein kinase B(Akt),caspase-3,Bax,Bcl-2,interleukin-8,and heat shock proteins.Immunohistochemical staining was performed for TLR2 and 4 and interleukin-8.Cells were also pretreated with OxPAPC,an antagonist of TLR2 and 4 to elucidate the molecular mechanism.Results showed that argon preconditioning before rotenone application caused a dose-dependent but not a time-dependent reduction in the number of apoptotic cells.Preconditioning with 74%argon for 2 hours was used for further experiments showing the most promising results.Argon decreased the surface expression of TLR2 and 4,whereas OxPAPC treatment partially abolished the protective effect of argon.Argon increased phosphorylation of ERK1/2 but decreased NF-κB and Akt.Preconditioning inhibited mitochondrial apoptosis and the heat shock response.Argon also suppressed the expression of the pro-inflammatory cytokine interleukin-8.Immunohistochemistry confirmed the alteration of TLRs and interleukin-8.OxPAPC reversed the argon effect on ERK1/2,Bax,Bcl-2,caspase-3,and interleukin-8 expression,but not on NF-κB and the heat shock proteins.Taken together,argon preconditioning protects against apoptosis of neuronal cells and mediates its action via Toll-like receptors.Argon may represent a promising therapeutic alternative in various clinical settings,such as the treatment of stroke. 展开更多
关键词 apoptosis inflammation INTERLEUKIN-8 neuroprotection ROTENONE SH-SY5Y toll-like receptor 2 toll-like receptor 4
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Toll-like receptor 2及其信号传导通路在阿片类物质诱导细胞凋亡中的作用
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作者 李艺 彭英 《重庆医科大学学报》 CAS CSCD 北大核心 2010年第9期1289-1294,共6页
目的:成瘾物质(Addictive drugs)导致的中毒性脑病的中枢神经系统损害以神经元凋亡为突出表现,具体机制仍有待进一步的研究探讨。方法:Toll-like receptor 2(TLR2)不仅是激活机体自身免疫防御和炎症反应的重要受体,而且广泛参与多种细... 目的:成瘾物质(Addictive drugs)导致的中毒性脑病的中枢神经系统损害以神经元凋亡为突出表现,具体机制仍有待进一步的研究探讨。方法:Toll-like receptor 2(TLR2)不仅是激活机体自身免疫防御和炎症反应的重要受体,而且广泛参与多种细胞功能,包括细胞凋亡。我们使用体外培养的HEK293和高表达TLR2的HEK2932种细胞,以及体外培养小鼠皮层原代神经元细胞,研究经过吗啡处理后细胞存活率和凋亡的变化,以探讨TLR2信号通路在吗啡诱导的细胞凋亡中的作用。结果:TLR2高表达导致吗啡诱导的细胞存活率下降和细胞凋亡的显著增加。使用MyD88抑制体竞争性抑制MyD88并阻断TLR2信号通路后,吗啡诱导的TLR2高表达细胞的凋亡也被明显抑制。长期的吗啡处理导致正常神经元的TLR2在信使RNA(mRNA)水平和蛋白水平表达明显增高,而且在TLR2功能缺失的原代神经元细胞中,吗啡诱导的caspase-3活性增高被阻断,吗啡诱导的神经元凋亡也被明显抑制。结论:TLR2信号通路参与吗啡诱导的神经元凋亡。 展开更多
关键词 中毒性脑病 toll-like receptor 2 吗啡 凋亡
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Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer 被引量:8
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作者 Karoliina Paarnio Sara Vayrynen +4 位作者 Kai Klintrup Pasi Ohtonen Markus J Makinen Jyrki Makela Tuomo J Karttunen 《World Journal of Gastroenterology》 SCIE CAS 2017年第26期4831-4838,共8页
To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. METHODSWe analysed tissue samples from a prospective series of 118 unselected surgically ... To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. METHODSWe analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed. RESULTSNormal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours. CONCLUSIONTumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease. 展开更多
关键词 Colorectal Cancer toll-like receptor 2 toll-like receptor 4 INFLAMMATION PROGNOSIS
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Protection against hepatic ischemia/reperfusion injury via downregulation of toll-like receptor 2 expression by inhibition of Kupffer cell function 被引量:9
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作者 Jin-Xiang Zhang He-Shui Wu +3 位作者 Yang Wang Hui Wang Jin-Hui Zhang Qi-Chang Zheng 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第28期4423-4426,共4页
AIM: To elucidate the mechanism of liver protection by inhibition of Kupffer cells (KCs) function.METHODS: All the animals were randomly divided into three groups. Blockade group (gadolinium chloride solution (G... AIM: To elucidate the mechanism of liver protection by inhibition of Kupffer cells (KCs) function.METHODS: All the animals were randomly divided into three groups. Blockade group (gadolinium chloride solution (GdCl3) injection plus ischemia/reperfusion (I/R) injury):GdCl3 solution was injected once every 24 h for 2 d via the tail vein before I/R injury. Non-blockade group (saline solution injection plus I/R injury): saline instead of GdCl3 as a control was injected as in the blockade group. Sham group: saline was injected without I/R injury. Liver samples were collected 4 h after blood inflow restoration. The blockade of the function of KCs was verified by immunostaining with an anti-CD68 mAb. Toll-like receptor2 (TLR2) was immunostained with a goat antimouse polydonal anti-TLR2 antibody. Membrane proteins were extracted from the liver samples and TLR2 protein was analyzed by Western blot. Portal vein serum and plasma were taken respectively at the same time point for further detection of the levels of tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), an indicator of liver function.I/R injury via downregulation of theexpression of TLR2.RESULTS: Compared to non-blockade group, CD^68+ cells significantly reduced in blockade group (OPTDI, optical density integral): 32.97±10.55 vs 185.65±21.88, P〈0.01) and the liver function impairment was relieved partially (level of ALT: 435.89±178.37 U/L vs 890.21±272.91 U/L,P〈0.01). The expression of TLR2 protein in blockade group significantly decreased compared to that in non- group(method of immunohistochemistry, OPDTI: 75.74±17.44 vs 170.58±25.14, P〈0.01; method of Western blot, A value: 125.89±15.49 vs 433.91±35.53, P〈0.02). The latter correlated with the variation of CD68 staining (r = 0.745,P〈0.05). Also the level of portal vein TNF-α decreased in blockade group compared to that in non-blockade group (84.45±14.73 ng/L vs 112.32±17.56 ng/L, P〈0.05), butwas still higher than that in sham group (84.45±14.73 ng/L vs 6.07±5.33 ng/L, P〈0.01).CONCLUSION: Inhibition of the function of KCs may protect liver against I/R injury via downregulation of the expression of TLR2. 展开更多
关键词 toll-like receptor 2 Reperfusion injury Kupffer cell LIVER
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Association between polymorphisms in the Toll-like receptor 4,CD14,and CARD15/NOD2and inflammatory bowel disease in the Greek population 被引量:17
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作者 Maria Gazouli Gerassimos Mantzaris +5 位作者 Athanassios Kotsinas Panayotis Zacharatos Efstathios Papalambros Athanassios Archimandritis John Ikonomopoulos Vassilis G Gorgoulis 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第5期681-685,共5页
AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune... AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune response such as CD14 or Toll-like receptor 4 (TLR4), are involved in their pathogenesis. In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp,Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.METHODS: DNA was obtained from 120 patients with CD,85 with UC and 100 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.RESULTS: The 299Gly allele frequency of the TLR4 gene and the T allele and TT genotype frequendes of the CD14 promoter were significantly higher in CD patients only compared to healthy individuals (P = 0.026<0.05; P = 0.0048<0.01 and P= 0.047<0.05 respectively). Concerning the NOD2/CARD15mutations the overall presence in CD patients was significantly higher than that in UC patients or in controls.Additionally, 51.67% of the CD patients were carriers of a TLR4 and/or CD14 polymorphic allele and at least one variant of the NOD2/CARD15, compared to 27% of the UC patients. It should be pointed out that both frequencies significantly increased as compared with the 10% frequency of multiple carriers found in healthy controls. A possible interaction of the NOD2/CARD15 with TLR4 and especially CD14, increased the risk of developing inflammatory bowel disease (IBD).CONCLUSION: Our results indicate that co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15is associated with an increased susceptibility to developing CD compared to UC, and to developing either CD or UC compared to healthy individuals. 展开更多
关键词 Inflammatory bowel disease CARD15/NOD2 gene toll-like receptor 4 CD14 Antigen
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Science Letters:A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen 被引量:6
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作者 Cheng ZHOU Xiao-dong KANG Zhi CHEN 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第4期279-285,共7页
It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported ... It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoidesfarinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-7 released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases. 展开更多
关键词 toll-like receptor 2 (TLR2 LIGAND Allergic immune response Mite allergen
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Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease 被引量:8
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作者 Luciana Rigoli Claudio Romano +12 位作者 Rosario Alberto Caruso Maria A Lo Presti Chiara Di Bella Vincenzo Procopio Giuseppina Lo Giudice Maria Amorini Giuseppe Costantino Maria D Sergi Caterina Cuppari Giovanna Elisa Calabrò Romina Gallizzi Carmelo Damiano Salpietro Walter Fries 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第28期4454-4461,共8页
AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, Gg08R an... AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, Gg08R and L1007finsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy. METHODS: Allele and genotype frequencies of NOD2/ CARD15 (R702W, Gg08R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS: NOD2/CARD15 R702W mutation was significantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No significant difference was found between UC patients and control group (P 〉 0.05). In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD (9.8%) compared with controls (2.9%, P = 0.002) and UC patients (2.3%, P = 0.01). Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05). CONCLUSION: These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD. 展开更多
关键词 Crohn's disease Ulcerative colitis NOD2/ CARD15 gene toll-like receptor 4 gene Single nucleotide polymorphisms
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Over-expression of Toll-like receptor 2 up-regulates heme oxygenase-1 expression and decreases oxidative injury in dairy goats 被引量:2
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作者 Shoulong Deng Kun Yu +8 位作者 Wuqi Jiang Yan Li Sutian Wang Zhuo Deng Yuchang Yao Baolu Zhang Guoshi Liu Yixun Liu Zhengxing Lian 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2017年第2期351-360,共10页
Background: Mastitis, an infection caused by Gram-positive bacteria, produces udder inflammation and oxidative injury in milk-producing mammals. Toll-like receptor 2(TLR2) is important for host recognition of invad... Background: Mastitis, an infection caused by Gram-positive bacteria, produces udder inflammation and oxidative injury in milk-producing mammals. Toll-like receptor 2(TLR2) is important for host recognition of invading Grampositive microbes. Over-expression of TLR2 in transgenic dairy goats is a useful model for studying various aspects of infection with Gram-positive bacteria, in vivo.Methods: We over-expressed TLR2 in transgenic dairy goats. Pam3CSK4, a component of Gram-positive bacteria,triggered the TLR2 signal pathway by stimulating the monocytes-macrophages from the TLR2-positive transgenic goats, and induced over-expression of activator protein-1(AP-1), phosphatidylinositol 3-kinase(PI3K) and transcription factor nuclear factor kappa B(NF-κB) and inflammation factors downstream of the signal pathway.Results: Compared with wild-type controls, measurements of various oxidative stress-related molecules showed that TLR2, when over-expressed in transgenic goat monocytes-macrophages, resulted in weak lipid damage, high level expression of anti-oxidative stress proteins, and significantly increased m RNA levels of transcription factor NF-E2-related factor-2(Nrf2) and the downstream gene, heme oxygenase-1(HO-1). When Pam3CSK4 was used to stimulate ear tissue in vivo the HO-1 protein of the transgenic goats had a relatively high expression level.Conclusions: The results indicate that the oxidative injury in goats over-expressing TLR2 was reduced following Pam3CSK4 stimulation. The underlying mechanism for this reduction was increased expression of the anti-oxidation gene HO-1 by activation of the Nrf2 signal pathway. 展开更多
关键词 Haem oxygenase Nrf2 signal pathway toll-like receptor 2 Transgenic goats
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Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody 被引量:8
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作者 Jiang NI Qing-Lei LI +2 位作者 Wei ZHANG Jian-Song XIE Shu-Ling BIAN Department of Physiology, Harbin Medical University, Harbin 150086, China 《Asian Journal of Andrology》 SCIE CAS CSCD 2000年第2期151-153,共3页
Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPas... Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb. 展开更多
关键词 male infertility antisperm antibodies soluble interleukin-2 receptor Na^+-K^+-exchanging ATPase
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Toll-like receptor expression and signaling in human diabetic wounds 被引量:2
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作者 Mohan R Dasu Sandra J Martin 《World Journal of Diabetes》 SCIE CAS 2014年第2期219-223,共5页
AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic p... AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic patients with informed consent. Total RNA and protein were isolated and subjected to real-time polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6 mRNA expressions were increased significantly in wounds of diabetic patients compared with non-diabetic wounds(P 【 0.05). MyD88 protein expression was significantly increased in diabetic wounds compared to non-diabetic wounds. Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa B activation, and thiobarbituric acid reactive substances were increased in diabetic wounds compared to non-diabetic wounds(P 【 0.01). CONCLUSION: Collectively, our novel findings show that increased TLR expression, signaling, and activation may contribute to the hyper inflammation in the human diabetic wounds. 展开更多
关键词 Interleukin-1;2 INFLAMMATION toll-like receptors 2 toll-like receptors 4 Tumor necrosis factor-α Type 2-diabetes mellitus Wound healing
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Effect of ω-3 Polyunsaturated Fatty Acid on Toll-like Receptors in Patients with Severe Multiple Trauma 被引量:2
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作者 易呈志 白祥军 +4 位作者 陈继革 陈驾君 李剑 刘鹏 廖忆刘 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第4期504-508,共5页
This study examined the effects of ω-3 polyunsaturated fatty acid(ω-3PUFA) on the expression of toll-like receptor 2(TLR2),toll-like receptor 4(TLR4) and some related inflammatory factors in peripheral blood m... This study examined the effects of ω-3 polyunsaturated fatty acid(ω-3PUFA) on the expression of toll-like receptor 2(TLR2),toll-like receptor 4(TLR4) and some related inflammatory factors in peripheral blood mononuclear cells(PBMCs) of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital(Wuhan,China) between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score(ISS) no less than 16,were enrolled in the study and divided into two groups at random(n=16 in each):ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission(day 0),and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support(both P0.05).The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day(P0.05 for all).It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway. 展开更多
关键词 ω-3 polyunsaturated fatty acid severe multiple trauma toll-like receptor 2 toll-like receptor 4
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靶向HER2胞外结构域Ⅳ的单克隆抗体在乳腺癌中的应用进展
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作者 徐娇娇 陶佳妮 +1 位作者 王晓稼 陈占红 《中国药房》 CAS 北大核心 2024年第5期635-640,共6页
人表皮生长因子受体2(HER2)阳性乳腺癌侵袭性强且易转移,抗HER2靶向药物的应用能显著改善HER2阳性乳腺癌患者的预后。在已上市的HER2靶向药物中,靶向HER2胞外结构域Ⅳ的大分子单克隆抗体是治疗HER2阳性乳腺癌的基础靶向药物,主要包括曲... 人表皮生长因子受体2(HER2)阳性乳腺癌侵袭性强且易转移,抗HER2靶向药物的应用能显著改善HER2阳性乳腺癌患者的预后。在已上市的HER2靶向药物中,靶向HER2胞外结构域Ⅳ的大分子单克隆抗体是治疗HER2阳性乳腺癌的基础靶向药物,主要包括曲妥珠单抗、伊尼妥单抗和马吉妥昔单抗。曲妥珠单抗用于乳腺癌全线治疗,循证医学证据充分,实践经验充足且安全性可控;伊尼妥单抗与曲妥珠单抗在HER2阳性转移性乳腺癌和新辅助/辅助治疗中疗效相似,且安全性可控;马吉妥昔单抗聚焦于携带CD16A-158F等位基因的患者,是晚期乳腺癌后线治疗的选择。临床上需根据患者具体病情选择最适合的药物。 展开更多
关键词 乳腺癌 人表皮生长因子受体2阳性 细胞外结构域Ⅳ 单克隆抗体 曲妥珠单抗 伊尼妥单抗 马吉妥昔单抗
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SARS-CoV-2广谱中和抗体性质鉴定
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作者 陈秀婷 汪毅祯 +2 位作者 商慧娴 王思令 郑子峥 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第4期693-697,共5页
目的:对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)广谱中和抗体XMA09进行性质鉴定,探究其广谱中和突变株的潜在机制,为SARS-CoV-2的疫苗设计与广谱中和抗体筛选提供参考。方法:通过ExpiCHO真核表达系统与Protein A层析柱表达纯化XMA09蛋... 目的:对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)广谱中和抗体XMA09进行性质鉴定,探究其广谱中和突变株的潜在机制,为SARS-CoV-2的疫苗设计与广谱中和抗体筛选提供参考。方法:通过ExpiCHO真核表达系统与Protein A层析柱表达纯化XMA09蛋白;冷冻电镜技术确定XMA09识别的受体结构域(RBD)上的关键氨基酸位点;间接ELISA与表面等离子共振(SPR)技术检测XMA09对SARS-CoV-2及其突变株Spike蛋白的亲和力;采用基于水疱性口炎病毒(VSV)的假病毒系统检测XMA09对SARS-CoV-2野生型及突变株的中和能力。结果:本研究发现XMA09识别的表位较为保守,对多种突变株Spike蛋白均具有强结合能力,能广谱中和关切突变株(VOCs),包括广泛流行的Omicron亚突变株BA.4/5。结论:XMA09是SARS-CoV-2广谱中和抗体,具有作为SARS-CoV-2治疗性抗体的潜力,并可为SARS-CoV-2的广谱疫苗设计与抗体药物开发提供参考意义。 展开更多
关键词 SARS-CoV-2 受体结合结构域(RBD) 广谱中和抗体
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Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis 被引量:1
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作者 Marnie J Wood Lawrie W Powell +2 位作者 Jeannette L Dixon V Nathan Subramaniam Grant A Ramm 《World Journal of Gastroenterology》 SCIE CAS 2013年第48期9366-9376,共11页
AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was... AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis. 展开更多
关键词 HAEMOCHROMATOSIS Genetic polymorphism Liver FIBROSIS toll-like receptor 4 Interleukin 10 Monocyte CHEMOATTRACTANT protein 1 Chemokine(C-C motif) ligand 2 Transforming growth factor beta 8-oxoguanine DNA GLYCOSYLASE
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抗体药物偶联物治疗HER-2阳性乳腺癌的机制与研究进展
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作者 裴家峤 张莹 +2 位作者 李子欣 冯曼曼 易丹 《临床医学研究与实践》 2024年第15期187-190,共4页
人表皮生长因子受体2(HER-2)阳性乳腺癌的诊治一直是乳腺癌领域的研究热点。单克隆抗体类药物和小分子酪氨酸激酶抑制剂的接连问世极大地改善了HER-2阳性乳腺癌患者的预后。然而,在极佳疗效的背后,靶向药物同样面临着多重耐药现象及心... 人表皮生长因子受体2(HER-2)阳性乳腺癌的诊治一直是乳腺癌领域的研究热点。单克隆抗体类药物和小分子酪氨酸激酶抑制剂的接连问世极大地改善了HER-2阳性乳腺癌患者的预后。然而,在极佳疗效的背后,靶向药物同样面临着多重耐药现象及心脏毒性等亟待解决的重大难题。近年来,随着HER-2阳性乳腺癌进入“精准分类,精确分层”的时代,抗体药物偶联物(ADC)成为肿瘤患者精准化治疗的热点领域之一。ADC通过特定的连接头将靶标特异性的单克隆抗体与高杀伤性的细胞毒性药物偶联起来,对肿瘤细胞具有高度特异性杀伤作用。本文就ADC的作用机制及其在HER-2阳性乳腺癌中的研究进展作一综述。 展开更多
关键词 抗体药物偶联物 靶向治疗 人表皮生长因子受体2 乳腺癌
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HER2阳性乳腺癌靶向治疗的研究进展
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作者 吴悠 戴建国 《中国临床新医学》 2024年第10期1183-1186,共4页
乳腺癌是全球女性发病率较高的恶性肿瘤,其中人类表皮生长因子受体2(HER2)阳性乳腺癌病例占总乳腺癌病例的20%~30%。与其他分子分型的乳腺癌比,HER2阳性乳腺癌预后更差,更易复发和转移。近年来,HER2阳性乳腺癌治疗备受关注,针对抗HER2... 乳腺癌是全球女性发病率较高的恶性肿瘤,其中人类表皮生长因子受体2(HER2)阳性乳腺癌病例占总乳腺癌病例的20%~30%。与其他分子分型的乳腺癌比,HER2阳性乳腺癌预后更差,更易复发和转移。近年来,HER2阳性乳腺癌治疗备受关注,针对抗HER2的靶向药物能显著改善HER2阳性乳腺癌患者的疗效。该文对HER2阳性乳腺癌靶向治疗的研究进展作一综述。 展开更多
关键词 乳腺癌 人类表皮生长因子受体2阳性 靶向治疗 分子机制 单克隆抗体
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