Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selective deficit in delayed hypersensitivity that characterizes anterior chamber-associated immune deviation (ACAID) is the direct result of a blood borne, Ag-specific, cell-associated signal that is created after Ag is injected into the anterior chamber of the eye of normal mice. The cells that carry this signal via the blood to the spleen express the mature macrophage marker F4/80 and are similar to, or perhaps even arise from, F4/80+ dendritic cells found within the stroma of normal iris and ciliary body. We have recently reported that ACAID-inducing properties can be conferred upon conventional F4/80-bearing macrophages harvested from the normal peritoneal cavity by incubating these cells in vitro with the soluble protein Ag, BSA, in the presence of supernatants harvested from cultured iris and ciliary body cells. Using this in vitro induction system, we have examined the limiting conditions for conferring ACAID-inducing potential on peritoneal exudate cells. We have found that an ACAID-inducing signal can be created in vitro with several different soluble Ag, including the retinal autoantigen-interphotoreceptor retinol binding protein, and that active endocytosis and processing by peritoneal exudate cells is required because chloroquine prevents these cells from acquiring ACAID-inducing properties. In addition, we have determined that for supernatant-treated peritoneal macrophages to induce ACAID to soluble Ag the cells must be 1) alive, 2) injected i.v. or i.p. (but not s.c.), and 3) administered to recipients with an anatomically intact spleen. When these conditions are met, as few as 20 F4/80+ macrophages pulsed with Ag in the presence of iris and ciliary body supernatants are sufficient to induce ACAID. Macrophage hybridomas derived from "conventional" APC can acquire ACAID-inducing potential in vitro if exposed to iris and ciliary body supernatants, whereas macrophage hybridomas derived from "suppressor inducer" APC constitutively possess ACAID-induced potential. Peritoneal macrophages that were endowed with ACAID-inducing properties by in vitro exposure to supernatants were found to elicit splenic suppressor cells similar to those found in spleens of mice with ACAID. Moreover, the expression of experimental autoimmune uveitis in mice immunized with interphotoreceptor retinol binding protein was significantly suppressed if the animals were pretreated with peritoneal exudate cells pulsed with this Ag in the presence of iris and ciliary body supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye. 138 41

Homeobox (Hox)-containing factors have been shown to play regulatory roles on lung development. Although HoxB3 gene expression is detected in the prenatal lung during development, its function has not been clarified precisely. We constructed an expression vector of a hamster HoxB3 coding region, which was cloned from hamster fetal lung cell line M3E3/C3. Sixteen-base deletion was found in the hamster HoxB3 coding sequence when compared with the mouse sequence. Under conditions of differentiation, cells transfected transiently with HoxB3 augmented the retinol-induced gene expression of Clara cell-specific secretory protein, whereas the cells showed reduced expression of surfactant-associated protein C. These alterations were attenuated by the transfection with HoxB3 antisense nucleotide. The results show that the cells with overexpressed HoxB3 were reinforced to have characteristics of Clara cells but did not have the characteristics of alveolar type II cells, and that HoxB3 played a stimulatory role on Clara cell differentiation in M3E3/C3 cells. In addition, the expression of Clara cell-specific secretory protein and surfactant-associated protein C genes was enhanced upon transfer of cells to collagen substrate, suggesting that collagen substrate has some regulatory functions on lung cell differentiation through cell adhesion.
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PMID:Increased gene expression of lung marker proteins in the homeobox B3-overexpressed fetal lung cell line M3E3/C3. 1197 19

Mutations in the APC (adenomatous polyposis coli) tumor suppressor gene cause uncontrolled proliferation and impaired differentiation of intestinal epithelial cells. Recent studies indicate that human colon adenomas and carcinomas lack retinol dehydrogenases (RDHs) and that APC regulates the expression of human RDHL. These data suggest a model wherein APC controls enterocyte differentiation by controlling retinoic acid production. However, the importance of APC and retinoic acid in mediating control of normal enterocyte development and differentiation remains unclear. To examine the relationship between APC and retinoic acid biosynthesis in normal enterocytes, we have identified two novel zebrafish retinol dehydrogenases, termed zRDHA and zRDHB, that show strong expression within the gut of developing zebrafish embryos. Morpholino knockdown of either APC or zRDHB in zebrafish embryos resulted in defects in structures known to require retinoic acid. These defects included cardiac abnormalities, pericardial edema, failed jaw and pectoral fin development, and the absence of differentiated endocrine and exocrine pancreas. In addition, APC or zRDHB morphant fish developed intestines that lacked columnar epithelial cells and failed to express the differentiation marker intestinal fatty acid-binding protein. Treatment of either APC or zRDHB morphant embryos with retinoic acid rescued the defective phenotypes. Downstream of retinoic acid production, we identified hoxc8 as a retinoic acid-induced gene that, when ectopically expressed, rescued phenotypes of APC- and zRDHB-deficient zebrafish. Our data establish a genetic link supporting a critical role for retinoic acid downstream of APC and confirm the importance of retinoic acid in enterocyte differentiation.
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PMID:Adenomatous polyposis coli control of retinoic acid biosynthesis is critical for zebrafish intestinal development and differentiation. 1535 64

Stellate cells are star-shaped cells located in the liver and mediate a multitude of primarily non-immunological functions. They play a pivotal role in the metabolism of vitamin A and store 80% of total body retinol. Upon activation, stellate cells differentiate to myofibroblasts for production of extracellular matrix, leading to liver fibrosis. Moreover, activated stellate cells regulate liver blood flow through vasoconstriction implicated in portal hypertension. Earlier work demonstrated stellate cell derived secretion of chemokines and cytokines such as transforming growth factor beta (TGF-beta), suggesting an association with immunological processes. Indeed, recent evidence indicated that hepatic stellate cells perform potent APC function for stimulation of NKT cells as well as CD8 and CD4 T cells. Additionally, stellate cell mediated antigen presentation induced protective immunity against bacterial infection. Current experiments reveal that the presenting ability of stellate cells is the key to antigen-dependent T cell instruction by vitamin A derived retinoic acid. Finally, future studies will show whether in the firmament of immunology stellate cells will represent fixed or falling stars.
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PMID:Starring stellate cells in liver immunology. 1806 43

Computed tomography (CT) scan is the mainstay for diagnosis of stroke; but the facility of CT scan is not easily available. A blood-based biomarker approach is required to distinguish ischemic stroke (IS) from hemorrhagic stroke (HS) in pre-hospital settings.To conduct a systematic review of diagnostic utility of blood biomarkers for differential diagnosis of stroke.A comprehensive literature search was carried out till March 7, 2017 in PubMed, Cochrane, Medline, OVID, and Google Scholar databases. Methodological quality of each study was assessed using the modified Quality Assessment of Diagnostic Accuracy Studies questionnaire.Eighteen studies were identified relevant to our systematic review. Ten single biomarkers and seven panels of different biomarkers were identified which showed potential for differentiating IS and HS. Activated Protein C- Protein C Inhibitor Complex (APC-PCI) (sensitivity-96%), Glial Fibrillary Acidic Protein (GFAP) (specificity-100%) and a panel of APC-PCI & GFAP (sensitivity- 71%) and Retinol Binding Protein 4 (RBP4) & GFAP (specificity- 100%) were found to have high sensitivity and specificity for differentiating the two stroke types.Our systematic review does not recommend the use of any blood biomarker for clinical purposes yet based on the studies conducted till date.
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PMID:Blood-based protein biomarkers for stroke differentiation: A systematic review. 2845 32