Title:
REGULATION OF CC CHEMOKINE RECEPTOR 3 (CCR3) EXPRESSION
Document Type and Number:
WIPO Patent Application WO2002062848
Kind Code:
A3
Abstract:
A method of regulating CCR3 expression by transcriptional and mRNA control. In one embodiment, regulation ossurs in a non-promoter, regulatory region of the CCR3 gene, such as untranslated exons 1, 2, and/or 3. This type of regulation has a preferential effect on eosinophilic cells; such selectivity advantageously produces less deleterious side effects when administered in a pharmaceutical prepearation. Regeulation of CCR3 expression by promoter targeting also presents a method to reduce CCR3 expression in a cell-specific or nonspecific manner. Other types of regulatory compounds do not semonstrate such a prefential effect. Because CCR3 is expressed on cells involved in inflammatory reactions, regulations of CCR3 provides an intervention site for asthma, as well as other allergic, inflammatory and hypersensitivity reactions, eosinophil-mediated diseases, and infectious disorders.
Inventors:
ROTHENBERG MARC E
ZIMMERMAN NIVES
ZIMMERMAN NIVES
Application Number:
PCT/US2002/003442
Publication Date:
February 06, 2003
Filing Date:
February 06, 2002
Export Citation:
Assignee:
CHILDRENS HOSP MEDICAL CENTER (US)
International Classes:
C07K14/715; C12N15/12; (IPC1-7): C07K14/715; C12N15/12
Domestic Patent References:
| WO1995012415A1 | 1995-05-11 |
Other References:
ZIMMERMANN N ET AL: "Analysis of the CC chemokine receptor 3 gene reveals a complex 5' exon organization, a functional role for untranslated exon 1, and a broadly active promoter with eosinophil-selective elements.", BLOOD. UNITED STATES 1 OCT 2000, vol. 96, no. 7, 1 October 2000 (2000-10-01), pages 2346 - 2354, XP002221611, ISSN: 0006-4971
YAMAGUCHI YUJI ET AL: "Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene.", BLOOD, vol. 91, no. 9, 1 May 1998 (1998-05-01), pages 3447 - 3458, XP002221612, ISSN: 0006-4971
YAMAMOTO KEIZO ET AL: "Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 8, 19 February 1999 (1999-02-19), pages 4646 - 4654, XP002221613, ISSN: 0021-9258
NIRODI CHAITANYA ET AL: "The role of CDP in the negative regulation of CXCL1 gene expression.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 28, 13 July 2001 (2001-07-13), pages 26122 - 26131, XP002221614, ISSN: 0021-9258
KAVANAUGH JESSICA L ET AL: "Analysis of the CCR3 promoter reveals cell-specific regulatory regions including GATA-1 sites in untranslated exon 1.", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 107, no. 2, February 2001 (2001-02-01), 57th Annual Meeting of the American Academy of Allergy, Asthma and Immunology;New Orleans, Louisiana, USA; March 16-21, 2001, pages S224, XP009001352, ISSN: 0091-6749
YAMAGUCHI YUJI ET AL: "Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene.", BLOOD, vol. 91, no. 9, 1 May 1998 (1998-05-01), pages 3447 - 3458, XP002221612, ISSN: 0006-4971
YAMAMOTO KEIZO ET AL: "Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 8, 19 February 1999 (1999-02-19), pages 4646 - 4654, XP002221613, ISSN: 0021-9258
NIRODI CHAITANYA ET AL: "The role of CDP in the negative regulation of CXCL1 gene expression.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 28, 13 July 2001 (2001-07-13), pages 26122 - 26131, XP002221614, ISSN: 0021-9258
KAVANAUGH JESSICA L ET AL: "Analysis of the CCR3 promoter reveals cell-specific regulatory regions including GATA-1 sites in untranslated exon 1.", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 107, no. 2, February 2001 (2001-02-01), 57th Annual Meeting of the American Academy of Allergy, Asthma and Immunology;New Orleans, Louisiana, USA; March 16-21, 2001, pages S224, XP009001352, ISSN: 0091-6749
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