Abstract/Details

C/EBPγ has a stimulatory role in the transcription of proinflammatory cytokine and chemokine genes


2009 2009

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Abstract (summary)

CCAAT/enhancer binding protein γ (C/EBPγ) is a ubiquitously expressed member of the C/EBP family of transcription factors that was originally described as an inhibitor of C/EBP transactivation potential. Previously, we reported that C/EBPγ augments the activity of C/EBPβ in lipopolysaccharide (LPS) induction of the interleukin-6 (IL-6) and IL-8 promoters in a B lymphoblast cell line. This ability of C/EBPγ to augment C/EBPβ transactivation potential is dependent upon its dimerization with C/EBPβ and is potentiated by coactivation of NF-κB. Here, we demonstrate a profound deficit in LPS-induced cytokine and chemokine expression in C/EBPγ-deficient mouse embryonic fibroblasts (MEFs) when compared to wild type (wt) MEFs. Chromatin immunoprecipitation analysis of two C/EBP target genes, IL-6 and IL-1β showed defective LPS-induced recruitment of C/EBPβ and C/EBPδ to the target promoters of these genes in C/EBPγ-deficient MEFs. These same promoters showed reduced LPS-induced NF-κB p65 occupancy. Furthermore, LPS-induced expression of several cytokine and chemokine genes was reduced in a tissue-specific manner in C/EBPγ-deficient mice when compared to wt mice. These findings demonstrate that C/EBPγ plays an important role in LPS-induced transcriptional activation of many cytokine and chemokine genes.

Indexing (details)


Subject
Genetics
Classification
0369: Genetics
Identifier / keyword
Biological sciences; Chemokines; Cytokines; Lipopolysaccharides; Proinflammatory
Title
C/EBPγ has a stimulatory role in the transcription of proinflammatory cytokine and chemokine genes
Author
Kadakia, Tejas B.
Number of pages
131
Publication year
2009
Degree date
2009
School code
0128
Source
DAI-B 71/02, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109643404
Advisor
Schwartz, Richard C.
University/institution
Michigan State University
University location
United States -- Michigan
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3396061
ProQuest document ID
304942033
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304942033
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