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Clinical and Vaccine Immunology, March 2006, p. 426-432, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.426-432.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

FoxA2 Involvement in Suppression of Protein C, an Outcome Predictor in Experimental Sepsis

David T. Berg,1 Bruce Gerlitz,1 Ganesh R. Sharma,1 Mark A. Richardson,1 Eddie J. Stephens,2 Renee L. Grubbs,2 Kimberly C. Holmes,2 Kelly Fynboe,2 Dominick Montani,2 Martin S. Cramer,1 Steven D. Engle,1 Joseph A. Jakubowski,1 Josef G. Heuer,1 and Brian W. Grinnell1*

Biotechnology Discovery Research,1 Pharmacology Core, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 462852

Received 9 September 2005/ Returned for modification 18 October 2005/ Accepted 21 December 2005

Low levels of protein C (PC) predict outcome as early as 10 h after insult in a rat polymicrobial sepsis model and were associated with suppression of PC mRNA, upstream transcription factor FoxA2, and cofactor hepatocyte nuclear factor 6 (HNF6). Small interfering RNA suppression of FoxA2 in isolated hepatocytes demonstrated regulation of both its cofactor HNF6 and PC. Our data suggest that reduced FoxA2 may be important in the suppression of PC and resulting poor outcome in sepsis.

* Corresponding author. Mailing address: Lilly Research Laboratories, Biotechnology Discovery Research, Lilly Corporate Center, Indianapolis, IN 46285. Phone: (319) 276-2293. Fax: (317) 277-2934. E-mail: bgrinnell{at}lilly.com.

Clinical and Vaccine Immunology, March 2006, p. 426-432, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.426-432.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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