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Originally published In Press as doi:10.1074/jbc.M206224200 on August 12, 2002

J. Biol. Chem., Vol. 277, Issue 41, 38827-38837, October 11, 2002
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C/EBPgamma Has a Stimulatory Role on the IL-6 and IL-8 Promoters*

Hongwei GaoDagger , Sara Parkin§, Peter F. Johnson§, and Richard C. SchwartzDagger

From the Dagger  Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320 and the § Eukaryotic Transcriptional Regulation Section, Regulation of Cell Growth Laboratory, NCI-Frederick, Frederick, Maryland 21702-1201

CCAAT/enhancer-binding protein gamma  (C/EBPgamma ) is an ubiquitously expressed member of the C/EBP family of transcription factors that has been shown to be an inhibitor of C/EBP transcriptional activators and has been proposed to act as a buffer against C/EBP-mediated activation. We have now unexpectedly found that C/EBPgamma dramatically augments the activity of C/EBPbeta in lipopolysaccharide induction of the interleukin-6 and interleukin-8 promoters in a B lymphoblast cell line. This activating role for C/EBPgamma is promoter-specific, neither being observed in the regulation of a simple C/EBP-dependent promoter nor the TNFalpha promoter. C/EBPgamma activity also shows cell-type specificity with no activity observed in a macrophage cell line. Studies with chimeric C/EBP proteins implicate the formation of a heterodimeric leucine zipper between C/EBPbeta and C/EBPgamma as the critical structural feature required for C/EBPgamma stimulatory activity. These findings suggest a unique role for C/EBPgamma in B cell gene regulation and, along with our previous observation of the ability of C/EBP basic region-leucine zipper domains to confer lipopolysaccharide inducibility of interleukin-6, suggest that the C/EBP leucine zipper domain has a role in C/EBP function beyond allowing dimerization between C/EBP family members.

* This research was supported by Grant-in-aid 9950490N (to R. C. S.) from the American Heart Association.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824-4320. Tel.: 517-355-6463, extension 1527; Fax: 517-353-8957; E-mail: schwart9@msu.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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