Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells. 2012

Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Dendritic cell (DC) homeostasis, like all mature blood cells, is maintained via hierarchal generation from hematopoietic precursors; however, little is known about the regulatory mechanisms governing DC generation. Here, we show that prostaglandin E(2) (PGE(2)) is required for optimal Flt3 ligand-mediated DC development and regulates expression of the Flt3 receptor on DC-committed progenitor cells. Inhibition of PGE(2) biosynthesis reduces Flt3-mediated activation of STAT3 and expression of the antiapoptotic protein survivin, resulting in increased apoptosis of DC-committed progenitor cells. Reduced DC development caused by diminished PGE(2) signaling is reversed by overexpression of Flt3 or survivin in DC progenitors and conversely is mimicked by STAT3 inhibition. PGE(2) regulation of DC generation is specifically mediated through the EP1 and EP3 G protein PGE(2) receptors. These studies define a novel DC progenitor regulatory pathway in which PGE(2) signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal DC progenitor survival and DC development in vivo.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077022 Survivin An apoptosis inhibitory protein that contains a single baculoviral IAP repeat (BIR) domain. It associates with MICROTUBULES and functions to regulate cell proliferation as a component of the chromosome passage protein complex (CPC), performing essential roles for localization of the complex, chromosome alignment, segregation during MITOSIS and CYTOKINESIS, and assembly of the MITOTIC SPINDLE. It is expressed by fetal kidney and liver cells and highly expressed in ADENOCARCINOMA and high-grade LYMPHOMA. BIRC5 Protein,Baculoviral IAP Repeat-containing Protein 5,Baculoviral IAP Repeat containing Protein 5

Related Publications

Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
June 1993, European journal of pharmacology,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
April 2008, The Journal of biological chemistry,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
December 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
April 2006, Allergy,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
June 2010, British journal of pharmacology,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
February 2014, Journal of immunology (Baltimore, Md. : 1950),
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
October 2004, Cancer letters,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
December 2000, Journal of immunology (Baltimore, Md. : 1950),
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
January 2017, Frontiers in pharmacology,
Pratibha Singh, and Jonathan Hoggatt, and Peirong Hu, and Jennifer M Speth, and Seiji Fukuda, and Richard M Breyer, and Louis M Pelus
February 2007, The Journal of experimental medicine,
Copied contents to your clipboard!