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Molecular and Cellular Biology, December 1998, p. 7269-7277, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

C/EBPalpha Is Critical for the Neonatal Acute-Phase Response to Inflammation

Bonnie L. Burgess-Beusse1 and Gretchen J. Darlington1,2,*

Department of Molecular and Human Genetics1 and Department of Pathology,2 Baylor College of Medicine, Houston, Texas 77030

Received 20 May 1998/Returned for modification 15 July 1998/Accepted 14 September 1998

Members of the C/EBP (CCAAT/enhancer binding protein) family of transcription factors play important roles in mediating the acute-phase response (APR), an inflammatory process resulting from infection and/or tissue damage. Among the C/EBP family of proteins, C/EBPbeta and -delta were thought to be the primary mediators of the APR. The function of C/EBPalpha in the APR has not been fully characterized to date. Here, we investigate the role of C/EBPalpha in the APR by using neonatal mice that lack C/EBPalpha expression. Northern blot analysis of acute-phase protein gene expression in neonatal mice treated with purified bacterial lipopolysaccharide or recombinant interleukin 1beta as an inflammation stimulus showed a strong APR in wild-type mice, but a response in C/EBPalpha null animals was completely lacking. The C/EBPalpha knockout and wild-type mice demonstrated elevations in C/EBPbeta and -delta mRNA expression and DNA binding as well as increased DNA binding of NF-kappa B, all of which are known to be important in the APR. Null mice, however, failed to activate STAT3 binding in response to lipopolysaccharide. Our results provide the first evidence that C/EBPalpha is absolutely required for the APR in neonatal mice, is involved in STAT3 regulation, and cannot be compensated for by other C/EBP family members.

* Corresponding author. Mailing address: Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 770-1868. Fax: (713) 770-1032. E-mail: gretchen{at}bcm.tmc.edu.

Molecular and Cellular Biology, December 1998, p. 7269-7277, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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