Functional characterization of human cysteinyl leukotriene 1 receptor gene structure. 2005

Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.

The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis. Cysteinyl leukotrienes (cysLTs), 5-lipoxygenase pathway products, are recognized now not only as important factors in asthmatic inflammation, but also as mediators of cell trafficking and innate immune responses. To study a role of cysLTs in inflammatory reactions we have characterized the gene structure of human cysteinyl leukotriene receptor type I (cysLT(1)R). The cysLT(1)R gene consists of 5 exons that are variably spliced and a single promoter region with multiple transcription start sites. Four different cysLT(1)R transcripts were identified. RT-PCR showed dominant and wide expression of the transcript I, containing exons 1, 4, and 5, with the strongest presence in blood leukocytes, spleen, thymus, lung, and heart. The expression of cysLT(1)R is functionally regulated at the transcriptional level by IL-4 through a STAT6 response element localized to the proximal cysLT(1)R promoter region. IL-4 stimulation increased cysLT(1)R mRNA (real-time PCR) and surface protein expression (flow cytometry) in a time-dependent fashion. CysLTs (LTD(4) and LTC(4)) induced an increased production of a potent monocyte chemoattractant CCL2 (MCP-1) in IL-4-primed THP-1 cells in a dose-dependent manner. This effect was effectively inhibited by the cysLT(1)R-selective antagonist MK571 in a dose-dependent manner and only partially by a nonselective cysLT(1)R/cysLT(2)R inhibitor BAY-u9773, implying a cysLT(1)R-mediated mechanism. Thus, cysLTs signaling through cysLT(1)R might contribute to inflammatory reactions by cooperating with IL-4 in enhanced CCL2 production in human monocytic cells.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
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
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015847 Interleukin-4 A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells. B-Cell Growth Factor-I,B-Cell Stimulatory Factor-1,Binetrakin,IL-4,Mast Cell Growth Factor-2,B Cell Stimulatory Factor-1,B-Cell Growth Factor-1,B-Cell Proliferating Factor,B-Cell Stimulating Factor-1,B-Cell Stimulatory Factor 1,BCGF-1,BSF-1,IL4,MCGF-2,B Cell Growth Factor 1,B Cell Growth Factor I,B Cell Proliferating Factor,B Cell Stimulating Factor 1,B Cell Stimulatory Factor 1,Interleukin 4,Mast Cell Growth Factor 2
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D050800 STAT6 Transcription Factor A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-4. Stat6 has been shown to partner with NF-KAPPA B and CCAAT-ENHANCER-BINDING PROTEINS to regulate GENETIC TRANSCRIPTION of interleukin-4 responsive GENES. STAT6 Protein,Signal Transducer and Activator of Transcription 6,Transcription Factor, STAT6

Related Publications

Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
February 2016, Scientific reports,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
September 2000, The Journal of biological chemistry,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
June 1999, Nature,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
January 2009, The European respiratory journal,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
June 2002, Life sciences,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
October 2001, Biochemical and biophysical research communications,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
November 2001, Biochemical pharmacology,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
December 2004, Journal of the American Academy of Dermatology,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
May 2001, Current protocols in pharmacology,
Grzegorz Woszczek, and Rafal Pawliczak, and Hai-Yan Qi, and Sahrudaya Nagineni, and Sura Alsaaty, and Carolea Logun, and James H Shelhamer
January 2014, Bioinformation,
Copied contents to your clipboard!