Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice.

Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Research Abstract Details 

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Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Abstract Text:

Ryotaro Sakamori,Tetsuo Takehara,Chihiro Ohnishi,Tomohide Tatsumi,Kazuyoshi Ohkawa,Kiyoshi Takeda,Shizuo Akira,Norio Hayashi,Ryotaro Sakamori,Tetsuo Takehara,Chihiro Ohnishi,Tomohide Tatsumi,Kazuyoshi Ohkawa,Kiyoshi Takeda,Shizuo Akira,Norio Hayashi,

Sepsis is an infection-induced syndrome with systemic inflammatory response leading to multiorgan failure and occasionally death. During this process, signal transducer and activator of transcription 3 (STAT3) is activated in the liver, but the significance of this molecule has not been established. We generated hepatocyte-specific STAT3-deficient mice (L-STAT3 KO) and examined the susceptibility of these mice to cecal ligation and puncture-induced peritonitis, a well-established septic model. L-STAT3 KO mice showed significantly higher mortality and produced lesser amounts of various acute phase proteins than control littermates. Although blood bacterial infection did not differ between L-STAT3 KO mice and control mice, the former showed deterioration of the systemic inflammatory response as evidenced by a significant increase in various cytokines such as tumor necrosis factor alpha, IFN-gamma, IL-6, IL-10, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1beta. A similar hyperinflammatory response was observed in another septic model caused by lipopolysaccharide (LPS) injection. In vitro analysis revealed that soluble substances derived from hepatocytes and dependent on STAT3 were critical for suppression of cytokine production from LPS-stimulated macrophage and splenocytes. CONCLUSION: STAT3 activation in hepatocytes can attenuate a systemic hyperinflammatory response and lethality in sepsis, in part by suppressing immune cell overactivation, implying a critical role of hepatocyte STAT3 signaling in maintaining host homeostasis.

Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Publishing Authors By Initials

R Sakamori,T Takehara,C Ohnishi,T Tatsumi,K Ohkawa,K Takeda,S Akira,N Hayashi,R Sakamori,T Takehara,C Ohnishi,T Tatsumi,K Ohkawa,K Takeda,S Akira,N Hayashi,

For similar pathological conditions, signs and symptoms: pathologic processes: inflammation: systemic inflammatory response syndrome research abstracts see: pathological conditions, signs and symptoms: pathologic processes: inflammation: systemic inflammatory response syndrome research

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Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Hepatology (Baltimore, Md.)

VOLUME: 46

Page Numbers: 1564-73

Journal Abbreviation: Hepatology

ISSN: 1527-3350

DAY: 18

MONTH: Nov

YEAR: 2007

Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Information

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LANGUAGE: eng

NlmUniqueID: 8302946

Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Keywords Mesh Terms:

KEYWORDS: Systemic Inflammatory Response Syndrome

MESH TERMS: pathology

Chemical & Substance for Abstract: Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. Information

Substance Name: Stat3 protein, mouse

Registry Number: 0

Grant and Affiliation Information for Signal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice.

AFFILIATION: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.

Country: United States

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MEDLINETA: Hepatology

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