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991.
《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer. 相似文献
992.
993.
Human defensins 总被引:7,自引:0,他引:7
Schneider JJ Unholzer A Schaller M Schäfer-Korting M Korting HC 《Journal of molecular medicine (Berlin, Germany)》2005,83(8):587-595
Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work 相似文献
994.
C. Sandler E. Ekokoski K. A. Lindstedt P. J. Vainio M. Finel T. Sorsa P. T. Kovanen L. M. Golub K. K. Eklund 《Inflammation research》2005,54(7):304-312
Objective: To find novel inhibitors of mast cell function we have studied the effect of a potent, non-antimicrobial, chemically modified tetracycline, CMT-3 or COL-3, on key functions of mast cells.Methods and Results: In the presence of 25 μM CMT-3, the 48/80-induced histamine release from rat serosal mast cells was inhibited significantly, to 43.0 ± 7.3% of control. Similarily, the activation-induced secretion of TNF-α and IL-8 by HMC-1 cells were decreased in the presence of 25 μM CMT-3 to 13.5 ± 4.1% and 9.7 ± 1.1% of control, respectively. CMT-3 did not cause intracellular accumulation of TNF-α but instead it reduced the expression of TNF-α mRNA in HMC-1 cells. Moreover, CMT-3 was found to significantly inhibit the protein kinase C (PKC) activity with IC50 value of 31 μM. CMT-3 inhibited effectively both human recombinant PKCalpha and PKCdelta isoforms. In comparison to doxycycline, CMT-3 was more effective as an inhibitor of both cytokine production and PKC activity.Conclusions: Considering the central role of PKC in mast cell activation, PKC inhibition could, at least partially, explain the observed inhibitory effects of CMT-3. The inhibition of the key proinflammatory functions of mast cells by CMT-3 suggests its potential clinical usefulness in the treatment of allergic and inflammatory disorders.Received 18 February 2005; returned for revision 7 March 2005; accepted by A. Falus 21 April 2005 相似文献
995.
鉴于热休克蛋白90β(hsp90β)基因内含子中含有维生素D3受体(VDR)结合位点,为探讨作为核受体家族成员的VDR是否对核受体特异分子伴侣的hsp90β基因的表达具有调控作用,我们开展了本项研究。分别将野生型VDR、含N端(1~133氨基酸残基)及C端(281~427氨基酸残基)片段的VDR突变体真核表达质粒与人hsp90β基因调控片段(-1039/+1531)介导的氯霉素乙酰基转移酶(CAT)报告基因质粒共转染Jurkat细胞,检测正常及经热休克(42℃,1h)处理后细胞裂解液中CAT活性。结果表明VDRN端增强、而C端抑制hsp90β的组成性表达;在热诱导条件下野生型VDR对hsp90β的表达有一定的抑制作用,而其C端片段的抑制较强。为进一步研究VDR对细胞内源性热休克基因表达的影响,我们用RTPCR方法研究了VDR的对细胞内hsp90β基因mRNA水平的影响,发现VDR过表达对hsp90β的热诱导表达明显抑制。结果提示VDR对hsp90β基因的组成性和热诱导表达的调控机制不同。 相似文献
996.
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes 总被引:28,自引:4,他引:28
Agata Yasutoshi; Kawasaki Akemi; Nishimura Hiroyuki; Ishida Yasumasa; Tsubat Takeshi; Yagita Hideo; Honjo Tasuku 《International immunology》1996,8(5):765-772
A mAb J43 has been produced against the product of the mousePD-1 gene, a member of the Ig gene superfamily, which was previouslyisolated from an apoptosis-induced T cell hybridoma (2B4.11)by using subtractive hybridization. Analyses by flow cytometryand immunoprecipitation using the J43 mAb revealed that thePD-1 gene product is a 50–55 kDa membrane protein expressedon the cell surface of several PD-1 cDNA transfectants and 2B4.11cells. Since the molecular weight calculated from the aminoacid sequence is 29,310, the PD-1 protein appears to be heavilyglycosylated. Normal murine lymphoid tissues such as thymus,spleen, lymph node and bone marrow contained very small numbersof PD-1+ cells. However, a significant PD-1+ population appearedin the thymocytes as well as T cells in spleen and lymph nodesby the in vivo anti-CD3 mAb treatment. Furthermore, the PD-1antigen expression was strongly induced in distinct subsetsof thymocytes and spleen T cells by in vitro stimulation witheither anti-CD3 mAb or concanavalin A (Con A) which could leadT cells to both activation and cell death. Similarly, PD-1 expressionwas induced on spleen B cells by in vitro stimulation with anti-IgMantibody. By contrast, PD-1 was not significantly expressedon lymphocytes by treatment with growth factor deprivation,dexamethasone or lipopolysaccharide. These results suggest thatthe expression of the PD-1 antigen is tightly regulated andinduced by signal transduction through the antigen receptorand do not exclude the possibility that the PD-1 antigen mayplay a role in clonal selection of lymphocytes although PD-1expression is not required for the common pathway of apoptosis. 相似文献
997.
Satoshi Yamagiwa Yuh Kuwano Katsuhiko Hasegawa Kazunari Sato Kazuo Ohtsuka Tsuneo Iiai Katsuhiro Tomiyama Hisami Watanabe Satoshi Sugahara Shuhji Seki Hitoshi Asakura Toru Abo 《European journal of immunology》1996,26(7):1409-1416
Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interleukin-2 receptor (IL-2R)βlo α? (possibly abnormal TCRint cells). The levels of TCRhi cells of thymic origin (generated through the mainstream of T cell differentiation in the thymus) profoundly decreased after the onset of disease. However, a small population of normal TCRint cells (i.e. IL-2Rβhi α?) were also found to exist in all tested organs. For example, the majority of abnormal IL-2Rβlo TCRint cells were CD4?8? CD2?, while normal IL-2Rβhi TCRint cells were a mixture of single-positive cells (mainly CD8+), CD4?8? cells and CD2+ cells. Moreover, normal TCRint cells preferentially produced normal Fas mRNA and Fas molecules from the lpr gene. This phenomenon explains the leaky appearance of normal Fas mRNA and Fas molecules in mice carrying the lpr gene. It is suggested that a small population of IL-2RβhiTCRint cells are resistant to the lpr genetic abnormality. 相似文献
998.
中药蜈蚣对小鼠胚胎发育的影响 总被引:2,自引:0,他引:2
孕鼠161只随机分组,在孕期第7-11天给实验组分别以500mg/(kg.d)(蜈蚣1组)及1000mg/(kg.d)(蜈蚣2组)的中药蜈蚣煎剂灌胃,至孕期18天记录各组孕鼠和胎鼠的发育情况。结果表明:蜈蚣1,2两组致畸作用明显,死胎,吸收胎比例升高;蜈蚣2组胎鼠和孕鼠的体重均下降,堕胎作用显著,与对照组比较,差异均有非常显著意义(P<0.01)。 相似文献
999.
Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides 总被引:7,自引:0,他引:7
The ability of five purified amphibian antimicrobial peptides (dermaseptin-1, temporin A, magainin I, and II, PGLa), crude peptide fractions isolated from the skin of Rana pipiens and R. catesbeiana, and four antimicrobial peptides (AMPs) from hybrid striped bass (piscidin-1N, -1H, -2, and -3) were examined for their ability to reduce the infectivity of channel catfish virus (CCV) and frog virus 3 (FV3). All compounds, with the exception of magainin I, markedly reduced the infectivity of CCV. In contrast to CCV, FV3 was 2- to 4-fold less sensitive to these agents. Similar to an earlier study employing two other amphibian peptides, the agents used here acted rapidly and over a wide, physiologically relevant, temperature range to reduce virus infectivity. These results extend our previous findings and strongly suggest that various amphibian and piscine AMPs may play important roles in protecting fish and amphibians from pathogenic viruses. 相似文献
1000.
Yanaba K Mukaida N Matsushima K Murphy PM Takehara K Sato S 《European journal of immunology》2004,34(12):3553-3561
The deposition of immune complexes induces an acute inflammatory response with tissue injury. Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple chemokines. To assess the role of the chemokine receptors CCR1 and CCR5, and a ligand for these receptors CCL3/macrophage inflammatory protein-1alpha, in this pathogenic process, the reverse passive cutaneous Arthus reaction was induced in mice lacking CCR1, CCR5, or CCL3. Edema was significantly attenuated in CCR1-deficient (CCR1(-/-)) and CCL3(-/-) mice but not CCR5(-/-) mice, compared with wild-type mice. Numbers of infiltrating neutrophils and mast cells were reduced in CCL3(-/-) and CCR1(-/-) mice, respectively, compared with wild-type mice. CCR1 and CCR5 were expressed on neutrophils and mast cells. Remarkably, the intradermal mRNA expression of CCL5/RANTES, another ligand for CCR1 and CCR5, was increased in CCR5(-/-) and CCL3(-/-) mice, compared with wild-type mice, while the cutaneous CCL3 mRNA expression was augmented in CCR1(-/-) and CCR5(-/-) mice. These results indicate that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus reaction, and also suggest that enhanced expression of CCL3 and CCL5 compensates for the loss of CCR1, CCR5, and CCL3 in the reaction. 相似文献