Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Expression of suppressors of cytokine signaling during liver regeneration.

Authors: Campbell, J S; Prichard, L; Schaper, F; Schmitz, J; Stephenson-Famy, A; Rosenfeld, M E; Argast, G M; Heinrich, P C; Fausto, N

Published In J Clin Invest, (2001 May)

Abstract: The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating liver are regulated by IL-6.

PubMed ID: 11375418 Exiting the NIEHS site

MeSH Terms: Animals; Antigens, CD/genetics; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Hepatectomy; Interleukin-6/immunology*; Liver Regeneration/immunology*; Mice; Mice, Knockout; Proteins/genetics*; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor/genetics; Repressor Proteins*; STAT3 Transcription Factor; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators/metabolism; Transcription Factors*; Tumor Necrosis Factor-alpha/immunology*

Back
to Top