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41.
Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo 总被引:7,自引:0,他引:7
Sandner SE Clarkson MR Salama AD Sanchez-Fueyo A Domenig C Habicht A Najafian N Yagita H Azuma M Turka LA Sayegh MH 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(6):3408-3415
Programmed death-1 (PD-1), an inhibitory receptor up-regulated on activated T cells, has been shown to play a critical immunoregulatory role in peripheral tolerance, but its role in alloimmune responses is poorly understood. Using a novel alloreactive TCR-transgenic model system, we examined the functions of this pathway in the regulation of alloreactive CD4+ T cell responses in vivo. PD-L1, but not PD-1 or PD-L2, blockade accelerated MHC class II-mismatched skin graft (bm12 (I-Abm12) into B6 (I-Ab)) rejection in a similar manner to CTLA-4 blockade. In an adoptive transfer model system using the recently described anti-bm12 (ABM) TCR-transgenic mice directly reactive to I-Abm12, PD-1 and PD-L1 blockade enhanced T cell proliferation early in the immune response. In contrast, at a later time point preceding accelerated allograft rejection, only PD-L1 blockade enhanced T cell proliferation. In addition, PD-L1 blockade enhanced alloreactive Th1 cell differentiation. Apoptosis of alloantigen-specific T cells was inhibited significantly by PD-L1 but not PD-1 blockade, indicating that PD-1 may not be the receptor for the apoptotic effect of the PD-L1-signaling pathway. Interestingly, the effect of PD-L1 blockade was dependent on the presence of CD4+ CD25+ regulatory T cells in vivo. These data demonstrate a critical role for the PD-1 pathway, particularly PD-1/PD-L1 interactions, in the regulation of alloimmune responses in vivo. 相似文献
42.
Funabashi H Ishikawa M Mie M Takahashi F Yanagida Y Aizawa M Kobatake E 《Biotechnology and bioengineering》2005,90(4):509-515
We developed an electrochemical detection method for evaluating cellular physiological status based on the stringent response as a means to monitor cell viability. A reporter plasmid was constructed by inserting the beta-galactosidase gene (lacZ) under the control of the rpoS promoter, and then used to transform E. coli cells. Electrochemical responses from the products catalyzed by beta-galactosidase expressed by these E. coli cells were detected using the chronoamperometric technique in a nondestructive manner. Comparisons of response currents between the relA-positive strain and relA-negative strain revealed that increases in these currents were caused by the stringent response due to the stressful alcoholic environment, and thus as a model of stressful cultivating conditions. The current was proportional to the beta-galactosidase activity assayed by a conventional method that required the destruction of cells. The cellular physiological status, which depends on the stringent response as a viability marker, therefore, could then be evaluated online with a current using the rpoS-lacZ reporter gene in the relA-positive strain without pretreatment. 相似文献
43.
Takasaki M Honma T Yanaka M Sato K Shinohara N Ito J Tanaka Y Tsuduki T Ikeda I 《The Journal of nutritional biochemistry》2012,23(6):640-645
Lipid metabolism in a child may be altered when the mother has a high-fat diet (HFD), but it is unclear whether the lipid metabolism of future offspring (grandchildren) is also changed under these circumstances. In this study, we examined the influence of intake of an HFD beyond one generation on offspring in normal mice. Parent mice fed an HFD were bred and the resultant second and third generations were also fed an HFD. The diets used in the study had approximately 20% more energy than a standard chow diet. Changes in lipid metabolism were examined in each generation. Intake of an HFD from generation to generation promoted lipid accumulation in the white adipose tissue of female mice, increased lipid, glucose and insulin levels in the serum, increased the activities of enzymes associated with fatty acid metabolism in the liver, promoted lipid accumulation in hepatocytes and adipocytes and increased the mRNA levels of Cdkn1a in the liver and white adipose tissue. These results suggest that activation of Cdkn1a promoted lipid accumulation in the liver and white adipose tissue of third-generation female mice that were offspring from earlier generations fed HFDs. Moreover, intake of a high-energy diet beyond one generation led to offspring with obesity, fatty liver and hyperinsulinemia. 相似文献
44.
Youji Nakagawa Toru Hasebe Miyuki Ishiai Hideki Yamamura Yuzuru Iimura Masayuki Hayakawa 《Bioscience, biotechnology, and biochemistry》2013,77(4):714-717
We constructed a plasmid that expresses FLO11 encoding a cell surface glycoprotein of Saccharomyces cerevisiae under the control of a constitutive promoter. This plasmid conferred pellicle-forming ability on the non-pellicle-forming industrial strain of S. cerevisiae at the air–liquid interface of the glucose-containing liquid medium. The induced pellicle-forming cells exhibited tolerance to furfural, which is a key toxin in lignocellulosic hydrolysates, in ethanol production. 相似文献
45.
Yamaguchi T Yamazaki T Inoue M Mashida C Kawagoe K Ogawa M Shiga S Nakagawa Y Kishimoto T Kurane I Ouchi K Ohzeki T 《FEMS immunology and medical microbiology》2005,43(1):21-27
Simkania negevensis has been associated with bronchiolitis in infants and community-acquired pneumonia in adults. Reports of exposure to this microorganism are only available from Israel, North America and Western Europe. Currently, no standard method for diagnosis of S. negevensis infection has been established nor have prevalence rates been shown in Japan. For the first time we demonstrated the ability of the microimmunofluorescence (MIF) test to detect S. negevensis-specific immunoglobulin G and exposure to S. negevensis in Japan. The positive rate in healthy volunteers was 4.3% (25/588), with rates increasing with age. Results indicate the usefulness of the MIF test as a serological method for detecting S. negevensis-specific antibodies. A standard serological test for infection with S. negevensis is needed. 相似文献
46.
47.
Adisak Tantiworawit Sujaree Khemakapasiddhi Thanawat Rattanathammethee Sasinee Hantrakool Chatree Chai-Adisaksopha Ekarat Rattarittamrong Lalita Norasetthada Pimlak Charoenkwan Somdet Srichairatanakool Kanda Fanhchaksai 《Bioscience reports》2021,41(2)
Hepcidin is a key iron-regulatory hormone, the production of which is controlled by iron stores, inflammation, hypoxia and erythropoiesis. The regulation of iron by hepcidin is of clinical importance in thalassemia patients in which anemia occurs along with iron overload. The present study aimed to evaluate the correlation between serum hepcidin and ferritin levels in thalassemia patients. This cross-sectional study investigated 64 patients with thalassemia; 16 β-thalassemia major (BTM), 31 β-thalassemia/hemoglobin (Hb) E (BE), and 17 Hb H + AE Bart’s disease (Hb H + AE Bart’s). The levels of serum hepcidin and ferritin, and Hb of the three groups were measured. The median values of serum ferritin and Hb were significantly different among the three groups, whereas serum hepcidin values were not observed to be significantly different. The correlation of the serum hepcidin and ferritin levels was not statistically significant in any of the three groups of thalassemia patients with BTM, BE, or Hb H + AE Bart’s (r = −0.141, 0.065 and −0.016, respectively). In conclusion, no statistically significant correlations were observed between serum hepcidin with any variables including serum ferritin, Hb, age, labile plasma iron (LPI), and number of blood transfusion units among the three groups of thalassemia patients. Likely, the regulation of hepcidin in thalassemia patients is affected more by erythropoietic activity than iron storage. 相似文献
48.
Yokoro M Suzuki M Yatani M Yamashita H Takahashi Y Tsuji H Kimoto M 《Bioscience, biotechnology, and biochemistry》2012,76(2):400-403
We produced a monoclonal antibody (mAb) against N(G),N(G)-dimethyl-L-arginine (asymmetric dimethylarginine: ADMA), an endogenous competitive inhibitor of nitric oxide synthase (NOS), and developed an enzyme-linked immunosorbent assay (ELISA). The competitive ELISA method using the mAb determined 5 nM-100 nM ADMA, and ADMA levels in human plasma and urine were found to be 0.78 μM and 51.3 μmol/g of creatinine respectively. 相似文献
49.
Kimura A Ohmichi M Tasaka K Kanda Y Ikegami H Hayakawa J Hisamoto K Morishige K Hinuma S Kurachi H Murata Y 《The Journal of biological chemistry》2000,275(5):3667-3674
Regulation of the mitogen-activated protein kinase (MAPK) family by prolactin-releasing peptide (PrRP) in both GH3 rat pituitary tumor cells and primary cultures of rat anterior pituitary cells was investigated. PrRP rapidly and transiently activated extracellular signal-regulated protein kinase (ERK) in both types of cells. Both pertussis toxin, which inactivates G(i)/G(o) proteins, and exogenous expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase I, which specifically blocks signaling mediated by the betagamma subunits of G proteins, completely blocked the PrRP-induced ERK activation, suggesting the involvement of G(i)/G(o) proteins in the PrRP-induced ERK activation. Down-regulation of cellular protein kinase C did not significantly inhibit the PrRP-induced ERK activation, suggesting that a protein kinase C-independent pathway is mainly involved. PrRP-induced ERK activation was not dependent on either extracellular Ca(2+) or intracellular Ca(2+). However, the ERK cascade was not the only route by which PrRP communicated with the nucleus. JNK was also shown to be significantly activated in response to PrRP. JNK activation in response to PrRP was slower than ERK activation. Moreover, to determine whether a MAPK family cascade regulates rat prolactin (rPRL) promoter activity, we transfected the intact rPRL promoter ligated to the firefly luciferase reporter gene into GH3 cells. PrRP activated the rPRL promoter activity in a time-dependent manner. Co-transfection with a catalytically inactive form of a MAPK construct or a dominant negative JNK, partially but significantly inhibited the induction of the rPRL promoter by PrRP. Furthermore, co-transfection with a dominant negative Ets completely abolished the response of the rPRL promoter to PrRP. These results suggest that PrRP differentially activates ERK and JNK, and both cascades are necessary to elicit rPRL promoter activity in an Ets-dependent mechanism. 相似文献
50.
Wakayama M Yada H Kanda S Hayashi S Yatsuda Y Sakai K Moriguchi M 《Bioscience, biotechnology, and biochemistry》2000,64(1):1-8
D-Aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (Alcaligenes A-6) was strongly inactivated by diethylpyrocarbonate (DEPC). An H67N mutant was barely active, with a kcat/Km 6.3 x 10(4) times lower than that of the recombinant wild-type enzyme, while the H67I mutant lost detectable activity. The H67N mutant had almost constant Km, but greatly decreased kcat. These results suggested that His67 is essential to the catalytic event. Both H69N and H69I mutants were overproduced in the insoluble fraction. The kcat/Km of H250N mutant was reduced by a factor of 2.5 x 10(4)-fold as compared with the wild-type enzyme. No significant difference between H251N mutant and wild-type enzymes in the Km and kcat was found. The Zn content of H250N mutant was nearly half of that of wild-type enzyme. These results suggest that the His250 residue might be essential to catalysis via Zn binding. 相似文献