Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The earliest T-precursor population in the adult murine thymus can give rise to dendritic cells (DC) in culture if stimulated with a cocktail of cytokines that includes interleukin (IL)-3, but not with cytokine mixes based on granulocyte-macrophage colony stimulating factor (GM-CSF), normally used to generate myeloid-derived DC. This and other evidence led to the proposal that two different lineages of DC exist, one lymphoid-related and the other myeloid-related. To determine whether this selective response to cytokines was restricted to murine DC, early human thymic T-precursors were isolated and their capacity to generate DC in response to various cytokines directly compared to their murine counterparts. In contrast to cultures of murine thymic precursors, CD34+CD1a- lineage marker negative (Lin-) precursor cells from the human thymus proliferated and generated DC with both the IL-3-containing cytokine mix lacking GM-CSF and with GM-CSF based cytokine mixes. These CD34+CD1a-Lin- human precursor cells also gave rise to NK cells under appropriate culture conditions, but produced no granulocyte, monocyte, eosinophil, megakaryocyte or erythroid cells in standard soft-agar colony-forming cell assays. Thus, although apparently lymphoid-restricted, the human thymic DC precursors responded to the myeloid factor GM-CSF as well as to the cytokines selective for murine lymphoid-related DC.
Cell Mol Biol (Noisy-le-grand) 2001 Feb
PMID:Development of dendritic cells in culture from human and murine thymic precursor cells. 1129 59

Inflammation is characterized by an interplay between pro- and anti-inflammatory cytokines. Cytokines are commonly classified in one or the other category: interleukin-1 (IL-1), tumor necrosis factor (TNF), gamma-interferon (IFN-gamma), IL-12, IL-18 and granulocyte-macrophage colony stimulating factor are well characterized as pro-inflammatory cytokines whereas IL4, IL-10, IL-13, IFN-alpha and transforming growth factor-beta are recognized as anti-inflammatory cytokines. In this review, we point out that this classification is far too simplistic and we provide numerous examples illustrating that a given cytokine may behave as a pro- as well as an anti-inflammatory cytokine. Indeed, the cytokine amount, the nature of the target cell, the nature of the activating signal, the nature of produced cytokines, the timing, the sequence of cytokine action and even the experimental model are parameters which greatly influence cytokine properties.
Cell Mol Biol (Noisy-le-grand) 2001 Jun
PMID:Pro- versus anti-inflammatory cytokines: myth or reality. 1150 77

Therion Biologics, the NCI and Aventis Pasteur are investigating CEA-TRICOM, a recombinant, pox virus-based vaccine that incorporates a triple dose of costimulatory molecules as well as the carcinoembryonic antigen (CEA) tumor antigen, for the potential treatment of colorectal cancer. CEA-TRICOM is designed to stimulate and strengthen the body's immune system to kill colorectal cancer cells. CEA-TRICOM is administered in a priming and boosting protocol using two unique pox virus vectors, rV-CEA-TRICOM (recombinant vaccinia vector) and rF-CEA-TRICOM (recombinant fowlpox vector). The TRICOM component of both rV-CEA-TRICOM and rF-CEA-TRICOM comprises three costimulatory molecule transgenes (B7-1, ICAM-1 and LFA-3) [414643], [414645], known to elicit strong cellular immune responses necessary for complete tumor destruction. In preclinical studies conducted by the NCI and Therion, researchers have demonstrated that this combination of three costimulatory molecules dramatically boosts the immune response to eradicate cancer in murine models [399610], [414631]. In February 2001, Therion Biologics and the NCI initiated a phase I trial of CEA-TRICOM [399610]. The phase I trial of CEA-TRICOM is designed to demonstrate proof-of-principle for using multiple costimulatory molecules in conjunction with a tumor antigen to improve the strength of cellular immune responses. It is a multistage, dose-escalation study that will assess the safety and immunologic effects of CEA-TRICOM in up to 42 patients who have advanced metastatic colorectal cancer. Subjects will receive rF-CEA-TRICOM alone, rV-CEA-TRICOM followed by booster vaccinations with rF-CEA-TRICOM or rV-CEA-TRICOM followed by rF-CEA-TRICOM and GM-CSF adjuvant. The primary measure of immune response will be the level of CEA-specific T-cells stimulated by vaccination, with levels of CEA-expressing tumor cells in the blood used as a potential secondary measure of treatment effect [399610].
Curr Opin Mol Ther 2001 Aug
PMID:Technology evaluation: CEA-TRICOM, Therion Biologics Corp. 1152 65

Pulmonary alveolar proteinosis (PAP) is a disorder that rapidly leads to respiratory failure, because the alveolar spaces fill with a lipid-rich, proteinaceous material that impedes gas exchange. The pathogenesis of this life-threatening process remained an enigma for decades. Recent analysis of the lung pathology and molecular genetics of affected families has provided a molecular basis for some cases of PAP-deficiency of surfactant protein SP-B. This lack result from mutations in the gene for SP-B. The common mutation, 121ins2, is present in about two-third of the patients with SP-B deficiency. Additional insights into the mechanism for this lipoproteinaceous accumulation within alveoli were contributed by serendipity in a granulocyte-macrophage colony stimulating factor (GM-CSF) knock-out mouse model developed to study basal hematopoiesis. In this model, hematopoiesis was unaffected, but the animals developed pulmonary alveolar proteinosis. Subsequently, mutations in the genes for GM-CSF or its receptor were identified as the cause for pulmonary alveolar proteinosis in some patients. In our review, we discuss the known clinical, pathologic, and molecular genetic aspects of pediatric PAP and consider avenues for future research.
Pediatr Pathol Mol Med
PMID:Pulmonary alveolar proteinosis: a review. 1155 40

Respiratory syncytial virus (RSV) is one of the principal agents of bronchiolitis and pneumonia in young children. Thus, there is a strong need to make a safe and effective vaccine against the RSV infection. DNA immunization is very effective at inducing both cellular and humoral immune responses. In this study, we inserted the RSV-F gene into expression vectors, pcDNA3.1 and pQE. These constructs were transformed into C2C12 and E. coli M15 cells, respectively. The expression of the RSV-F protein was confirmed by SDS-PAGE, followed by Western blot analyses. The immunization of pcDNA3.1-RSV-F elicited both anti-RSV-F titer in mouse sera and CTL activities with mouse splenocytes. Especially, the co-administration of IL-4, or the GM-CSF gene with the RSV-F gene construct, enhanced the production of anti-RSV-F Ab. However, this enhancement disappeared by the simultaneous injection of the Th1 and Th2 type cytokine genes. The CTL activities were affected by the co-delivery of the IFN-gamma gene, but not by Th2-type cytokines.
Mol Cells 2001 Aug 31
PMID:Immune induction and modulation in mice following immunization with DNA encoding F protein of respiratory syncytial virus. 1156 30

Immortalized cloned human chondrocytes isolated from a normal (Ch-4, 8, N) and an osteoarthritis patient (Ch-8-OA) were established by introduction of recombinant SV40-adenovirus vector containing SV40 early gene. These cells exhibited continuous proliferative capacity in monolayer culture and showed chondrocytic characteristics in that they were positive for alkaline phosphatase and collagen type II. When cells were treated with IL-1alpha, the growth was inhibited. IL-1alpha induced the production of IL-6, GM-CSF and TNFalpha from immortalized chondrocytes. Significantly high amounts of cytokines including IL-6, GM-CSF and TNFalpha were produced from Ch-8-OA cells, even in the absence of IL-1alpha stimulation. Interestingly, TNFalpha, exogenously added into the culture, inhibited the growth of Ch-8-OA cells. Further studies are required to clarify the different mechanisms on chondrocytes originating from osteoarthritis cartilage underlying the biological reaction to various cytokines and the production of these cytokines as compared with chondrocytes from normal cartilages. However, the novel chondrocyte cell lines established in the present study may provide researchers with a useful model for studying the pathogenesis of osteoarthritis.
Int J Mol Med 2001 Oct
PMID:Characterization of immortalized human chondrocytes originated from osteoarthritis cartilage. 1156 70

We have recently demonstrated that the gene encoding the osteopontin (OPN) protein is activated both by interleukin-3 and granulocyte-macrophage colony-stimulating factor signaling pathways and that, through binding to the cell surface receptor CD44, OPN contributes to the survival activities of interleukin (IL)-3 and GM-CSF (Lin, Y.-H., Huang, C.-J., Chao, J.-R., Chen, S.-T., Lee, S.-F., Yen, J. J.-Y., and Yang-Yen, H.-F. (2000) Mol. Cell. Biol. 20, 2734-2742). In this report, we demonstrate that the CD44-binding domain of OPN involves a region containing amino acid residues from 121 to 140 and that both threonine and serine at positions 137 and 147, respectively, are essential for the survival stimulatory effect of OPN. Substitution of either residue with alanine results into a dominant negative mutant that overrides the survival effect of IL-3. Upon binding to the CD44 receptor, the wild-type OPN but not the inactive mutant induces activation of phosphatidylinositol 3-kinase and Akt. Last, we demonstrate that two waves of Akt activation are detected in IL-3-treated cells and that the survival promoting effect of OPN is mediated predominantly through the phosphatidylinositol 3-kinase/Akt signaling pathway. Together, our results suggest that a positive autoregulatory loop is involved in the survival pathway of IL-3.
 ...
PMID:The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. 1159 Jan 66

Six mAbs were raised against human "functionally inactive" recombinant IL-18, ELISA for determination of "functionally inactive" forms of IL-18 were established using two of these mAbs (#21 and #132), and inactive species of IL-18 protein were examined with human blood plasma and macrophages (Mp). In 6-day GM-CSF-treated monocytes, namely Mp, the mAb #21 recognized the IL-18 proform (24 kDa) and a 48 kDa dimer by immunoblotting. In contrast, only the 24 kDa species was detected as a relatively faint band with a commercial mAb against "active" IL-18. No IL-18 species was detected in premature monocytes. Thus, the dimeric IL-18 was produced in Mp and detectable with the mAb we established. In blood plasma of normal subjects and patients, the #21-recognizable IL-18 was also detected by ELISA, the levels of which were not consistent with those obtained with the commercially available kit for determination of "functionally active" IL-18. We designated the former as type 2 and the latter as type 1. Strikingly, IL-18 type 1 was detected in all volunteers while type 2 was detected in approximately 30% of healthy subjects, and the levels of type 2 were high (10-100 ng/ml) compared to those of type 1 (0.02-0.55 ng/ml) in their blood plasma. In patients with atopic dermatitis, the mean value of type 1 was high (200 ng/ml) compared to those of normal subjects (0.122 ng/ml) and patients with lung cancer (0.113 ng/ml). Production of high type 1 may be associated with an immunomodulatory state in atopic dermatitis. The levels and frequencies of IL-18 type 2 were not significantly changed among these populations. Hence, large amounts of type 2 species are produced in monocyte-Mp differentiation, and their levels and frequencies are unchanged in blood plasma irrespective of the levels of type 1.
Int J Mol Med 2001 Nov
PMID:Protein polymorphism of human IL-18 identified by monoclonal antibodies. 1160 32

We evaluated the efficiency of recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) as a tumor vaccine in an immunocompetent mouse model of head and neck squamous cell carcinoma (SCC VII/SF). Mice with five-day-old tumors in the floor of the mouth were treated with rvv-IL-2 by intratumoral injections. These treated mice survived longer (P <.03) than mice treated with control vaccines. Splenocytes, bone marrow, and lymph node cells from tumor-bearing mice responded poorly to concanavalin A stimulation, suggesting induction of immunosuppression. The rvv-IL-2 virus grew for 7 days in the tumor following intratumoral injection. We did not detect any virus particles in several normal organs following rvv-IL-2 injection. Comparison of expression levels of several potential immune inhibitory mediators between the tumors growing in mice and cultured tumor cells demonstrated higher expression of IL-10, GM-CSF, TGF-beta, and NO synthetase in tumors. These results suggested possible roles for these molecules in immunosuppression. We conclude that rvv-IL-2 has potential as a therapeutic vaccine for head and neck cancer and that it can be more effective provided the immunosuppression is reversed.
Mol Ther 2001 Dec
PMID:Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression. 1173 39

Elevated levels of exhaled nitric oxide are seen in inflammatory airway diseases such as asthma, but the cellular source remains unknown. This study investigated whether human airway epithelial cells express inducible nitric oxide synthase (iNOS). Human bronchial epithelial cells stimulated with 50 ng/ml interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma express iNOS mRNA, protein and increased nitrite in the cell culture media, which was inhibited by the selective iNOS inhibitor 1400W. Cells derived from subjects with asthma produced less nitrite than cells from normal subjects (6.59 +/- 0.99 microM nitrite, n = 15 versus 3.89 +/- 0.42 microM nitrite, n = 20; P < 0.05). This was not attributed to steroid treatment of subjects with asthma because there was no difference in the amount of nitrite released from steroid-naive and steroid-treated cells (3.51 +/- 0.46 versus 4.27 +/- 0.7 microM nitrite, n = 10). Neither dexamethasone nor budesonide inhibited iNOS mRNA induction, protein expression, or nitrite accumulation. The cells were not steroid insensitive because steroids inhibited GM-CSF release. Therefore, although these cells express iNOS under inflammatory conditions, they do not appear to be regulated directly by glucocorticosteroids.
Am J Respir Cell Mol Biol 2002 Jan
PMID:Expression and regulation of inducible nitric oxide synthase from human primary airway epithelial cells. 1175 Dec 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>