Abstract:
:Even though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0.00013 microM) and PDE7A with low potency (IC50 = 1.7 microM) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 microM. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Nakata A,Ogawa K,Sasaki T,Koyama N,Wada K,Kotera J,Kikkawa H,Omori K,Kaminuma Odoi
10.1046/j.1365-2249.2002.01856.xsubject
Has Abstractpub_date
2002-06-01 00:00:00pages
460-6issue
3eissn
0009-9104issn
1365-2249pii
1856journal_volume
128pub_type
杂志文章abstract::A new antimitochondrial antibody (AMA) against an outer membrane associated antigen on liver mitochondria was detected by ELISA in sera from patients with primary biliary cirrhosis (PBC). This antibody was named anti-M9. There is evidence that it is a partial organ-specific antibody as shown by absorption studies usin...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1995.tb08363.x
更新日期:1995-08-01 00:00:00
abstract::The mechanism of disease progression in Hashimoto's thyroiditis (HT) is still unclear. Anti-thyroid peroxidase antibody (TPOAb), a diagnostic hallmark of HT, is principally of the immunoglobulin G (IgG) isotype, and it appears to be a response to thyroid injury. The aim of our study was to evaluate the distribution of...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2008.03756.x
更新日期:2008-11-01 00:00:00
abstract::We have studied immunological, serological and clinical abnormalities in 264 HIV-positive and HIV-negative drug abusers. Ninety percent of the 264 drug addicts (mean age 26 +/- 0.8 years) were found to have HIV antibodies and there was a significant increase (P less than 0.01) in the frequency of HIV antibody positivi...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Thymic stromal lymphopoietin (TSLP) is known for its capacity to induce CD11c(+) myeloid dendritic cells to promote T helper type 2 (Th2)-skewed inflammatory responses. Although increased expression of TSLP was reported in the lesional skin of limited numbers of patients with atopic dermatitis (AD), the relationships...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12021
更新日期:2013-03-01 00:00:00
abstract::Complement plays important roles in host immune defences, and recent studies suggest that adipose tissue is an important site of production for some complement proteins. Starvation has been associated with low complement levels, but studied populations have usually had concomitant opportunistic infections or other con...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1997.3921287.x
更新日期:1997-06-01 00:00:00
abstract::Inhibitors of cyclic nucleotide phosphodiesterases are known to suppress lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production in vitro in human monocytes. The most potent of these have selectivity for type IV PDEs, suggesting that this class of PDE is the major type involved in the regu...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1995.tb03613.x
更新日期:1995-04-01 00:00:00
abstract::A previously unrecognized autoantibody, detected by immunofluorescence, reacted with all human organs but gave negative results on tissues from rat, mouse, rabbit, guinea-pig, calf and chicken. From its predilection for mitochondria-rich cells (oncocytes) and its selective absorption with human but not animal mitochon...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::Nitric oxide (NO) is a mediator of inflammatory injury which is inhibited by glucocorticoids and is implicated in rheumatoid (RA) and adjuvant arthritis (AA). The glucocorticoid-induced anti-inflammatory molecule lipocortin 1 is expressed in RA synovium, but the effects of lipocortin 1 on synovial inflammation have be...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1998.00438.x
更新日期:1998-01-01 00:00:00
abstract::Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Recently, a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds FasL and inhibits FasL-induced apoptosis, has...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.2000.01132.x
更新日期:2000-02-01 00:00:00
abstract::Increasing evidence has demonstrated that the immune system closely interacts with other physiological systems, whose communications are mediated by circulating cytokines and hormones. The aim of our study was to test whether the number and cytolytic activity of NK cells in a group of relatively healthy Italian nonage...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1999.00855.x
更新日期:1999-04-01 00:00:00
abstract::Monoclonal anti-dermatan sulphate antibodies were produced with hybridization after immunizing BALB/c mice with dermatan sulphate (DS). These antibodies were tested for cross-reactivity to double-stranded DNA (dsDNA) and heat-denatured DNA (ssDNA). Five clones had binding activity to DS, dsDNA and ssDNA in enzyme-link...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::The effects of surgery on the immune response (as measured by a variety of parameters) were examined in patients undergoing transurethral resection of the prostate (TURP) for benign disease. Two groups were assessed, one having the procedure performed under a general anaesthetic and the other under a spinal anaestheti...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1982-06-01 00:00:00
abstract::Serum specimens from 66 HIV-1-infected subjects were tested by ELISA for the presence of IgA antibodies to HIV-1: 44 samples were found positive and 37 were confirmed by immunoblot. In these subjects, the presence of anti-HIV IgA antibodies was studied in relation to the total count of circulating CD4+ lymphocytes and...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1993.tb05889.x
更新日期:1993-02-01 00:00:00
abstract::Lymphocyte subpopulations in patients with cervical carcinoma were studied before and after radiotherapy. T lymphocytes were recognized by their ability to form spontaneous rosettes with sheep erythrocytes (E rosettes). Two surface marker characteristics were used to detect B lymphocytes: receptors for activated compl...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::Using immunofluorescence forty-nine sera giving striational staining of skeletal and cardiac muscle have been tested on glycerinated myofibrils. By comparing immunofluorescence and phase contrast it has been found that these antibodies are rather heterogeneous but at least three different staining patterns can be iden...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Autoantibodies directed against the Sm proteins of the spliceosome complex are found in approximately 25% of systemic lupus erythematosus (SLE) patients sera. To determine which regions of the Sm D polypeptide are involved in the lupus autoimmune response, binding to overlapping octapeptides of Sm D has been evaluated...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1994.tb05507.x
更新日期:1994-12-01 00:00:00
abstract::Previous studies have shown that rabbit anti-mouse immunoglobulin sera (anti-Ig) which kill non-activated B lymphocytes in the presence of complement, are incapable of doing so when the cells are activated by antigen or mitogen into mitosis. Results reported here indicate that the resistance is not dependent on either...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1975-04-01 00:00:00
abstract::The level and avidity of anti-DNA antibody in the serum of New Zealand Black/White (NZB/W F1) hybrid mice has been determined. The results show that there is an age and sex-related variation in the avidity of this antibody. In mice of both sexes, the avidity of circulating anti-DNA antibody increases up to 5 months of...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
abstract::Kawasaki disease (KD) is an acute febrile illness of early childhood, in which the activation of monocytes/macrophages plays a central role in the development of vasculitis during the acute stage of disease. In this study we investigated peripheral blood T cells of 10 patients with KD, focusing on the Th1 and Th2 imba...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1999.00899.x
更新日期:1999-06-01 00:00:00
abstract::Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developin...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12858
更新日期:2016-12-01 00:00:00
abstract::We have compared features of experimental thyroiditis in the Buffalo strain rat induced by neonatal thymectomy, immunization with rat thyroglobulin (Tg) and complete Freund's adjuvant, and subcutaneous administration of trypan blue or 3-methylcholanthrene. The disease produced by neonatal thymectomy resulted in signif...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::New antibodies against a U3 snRNP, which were named anti-Myo 22/25 antibodies, were detected in four (8%) of 53 serum samples from patients with polymyositis/dermatomyositis (PM/DM) by RNA immunoprecipitation. In the protein immunoprecipitation analysis, all four serum samples precipitated 22 kDa and 25 kDa proteins, ...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.2001.01650.x
更新日期:2001-11-01 00:00:00
abstract::The lymph nodes of mice overloaded with mycobacterial products, either by the injection of whole or ultrasonicated organisms, or as a consequence of severe infection with Mycobacterium ulcerans, contain phagocytic cells which cause spontaneous transformation of the lymph node cells in a low volume, high cell density c...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
abstract::Aspergillus fumigatus, a ubiquitous fungus, is implicated in the pathogenesis of a number of clinically different allergic diseases in man, including allergic bronchopulmonary aspergillosis. Peptide-based immunotherapy may offer an alternative treatment strategy for the management of allergic disease. The objective of...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.2002.01776.x
更新日期:2002-02-01 00:00:00
abstract::Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for HMGB1 and might be ...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12951
更新日期:2017-06-01 00:00:00
abstract::In this study, we examined the effect of ethyl pyruvate (EP) on pulmonary inflammation in rats with severe pancreatitis-associated acute lung injury (ALI). Severe acute pancreatitis (SAP) was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12062
更新日期:2013-06-01 00:00:00
abstract::Adult-onset Still's disease (AOSD) patients may show an evanescent salmon-pink erythema appearing during febrile attacks and reducing without fever. Some patients may experience this eruption for many weeks. During AOSD, exceptionally high serum levels of ferritin may be observed; it is an iron storage protein compose...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12826
更新日期:2016-10-01 00:00:00
abstract::Immunofluorescence (IF) to detect HCV antigens and non-isotopic in situ hybridization (NISH) to detect HCV RNA genome were carried out on bone marrow (BM) and peripheral blood (PB) mononuclear cells (MC) of 11 chronically HCV-infected patients. In four patients (36.4%) HCV antigens were detected in monocytes/macrophag...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1996.tb08296.x
更新日期:1996-03-01 00:00:00
abstract::Organ transplantation is the treatment of choice for patients with end-stage organ failure, but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore, a drug-free state would be desirable where the recipient permanently accepts a donor organ while...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章,评审
doi:10.1111/cei.12976
更新日期:2017-08-01 00:00:00