期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 107, 期 10, 页码 1285-1292出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI11867
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资金
- NCI NIH HHS [R01 CA074131, R01 CA023226, R37 CA023226, CA-74131] Funding Source: Medline
- NIAID NIH HHS [AI-23226] Funding Source: Medline
- NIDDK NIH HHS [F32 DK009920, F32-DK09920-01] Funding Source: Medline
- NIEHS NIH HHS [T32-ES07032-23, T32 ES007032] Funding Source: Medline
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 cyokine signaling (SOCS) maybe involved in terminating LL-G 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.
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