Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Hepatocytes synthesize acute-phase proteins during inflammation.
• Interleukin-6 (IL-6) and related cytokines mediate the hepatic acute-phase response.
• These mediators belong to the hematopoietic family of alpha-helical cytokines.

Purpose of the Study:

• To investigate the role of ciliary neurotrophic factor (CNTF) in the hepatic acute-phase response.
• To identify the receptor components utilized by CNTF on hepatic cells.

Main Methods:

• Utilized human hepatoma cells (HepG2, Hep3B) and primary rat hepatocytes.
• Administered CNTF and measured induction of acute-phase protein genes (haptoglobin, alpha 1-antichymotrypsin, alpha 2-macroglobulin, beta-fibrinogen).
• Employed cell-free binding assays to assess CNTF receptor interactions and utilized cell lines lacking specific receptors (leukemia inhibitory factor receptor).

Main Results:

• CNTF induced hepatic acute-phase protein genes in HepG2 cells and primary rat hepatocytes with dose-response and time-course comparable to IL-6.
• CNTF did not bind to the 80 kDa IL-6 receptor.
• CNTF failed to induce acute-phase protein synthesis in Hep3B cells lacking the leukemia inhibitory factor receptor.

Conclusions:

• CNTF is a novel mediator of the hepatic acute-phase response.
• The leukemia inhibitory factor receptor is likely a component of the functional CNTF receptor on hepatic cells.
• CNTF's action on liver cells is distinct from IL-6 signaling pathways.