Expression of suppressors of cytokine signaling during liver regeneration
| Autor: | Lisa Prichard, Jean S. Campbell, Nelson Fausto, Peter C. Heinrich, Jochen Schmitz, Fred Schaper, Maryland E. Rosenfeld, Alyssa Stephenson-Famy, Gretchen M. Argast |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
STAT3 Transcription Factor
inorganic chemicals medicine.medical_treatment Suppressor of Cytokine Signaling Proteins Biology behavioral disciplines and activities Receptors Tumor Necrosis Factor Article Mice Antigens CD otorhinolaryngologic diseases medicine Animals Hepatectomy Receptor Transcription factor Mice Knockout Interleukin-6 Tumor Necrosis Factor-alpha Proteins General Medicine Molecular biology Liver regeneration Liver Regeneration DNA-Binding Proteins Repressor Proteins Cytokine Gene Expression Regulation Receptors Tumor Necrosis Factor Type I Suppressor of Cytokine Signaling 3 Protein Trans-Activators Phosphorylation Tumor necrosis factor alpha sense organs Signal transduction psychological phenomena and processes Signal Transduction Transcription Factors |
| Zdroj: | Journal of Clinical Investigation. 107:1285-1292 |
| ISSN: | 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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