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Ann N Y Acad Sci. 2003 Apr;987:280-4.

A genome-wide analysis of the acute-phase response and its regulation by Stat3beta.

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  • 1Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.


The acute-phase response (APR) is the systemic inflammatory component of innate immunity. A global assessment of hepatic gene expression during an APR has been undertaken. In response to endotoxin, an inducer of the APR, about 7% of mouse genes exhibited significant changes in expression. Genes for cholesterol, fatty acid, and phospholipid synthesis were suppressed, while genes participating in innate defense and antigen presentation were induced. Upon challenge with endotoxin, mice deficient in Stat3beta, a dominant-negative variant of Stat3, exhibited impaired recovery and susceptibility to protracted shock. These findings are accompanied by overexpression and hyperresponsiveness of a subset of lipopolysaccharide (LPS)-inducible genes in liver, suggesting a critical role for Stat3beta in the control of systemic inflammation.

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