Kupffer cell-dependent signaling in thyroid hormone calorigenesis: Possible applications for liver preconditioning

Abstract

Thyroid hormone (L-3,3′,5-triiodothyronine, T3) is important for the normal function of most tissues, with major actions on O2 consumption and metabolic rate. In the liver, these are due to (i) transcriptional activation of respiratory genes leading to increased reactive O2 species generation in mitochondria and other subcellular sites; and (ii) enhancement in the respiratory burst activity in Kupffer cells (KC), with consequent antioxidant depletion. Under these conditions, the redox upregulation of KC-dependent expression of cytokines (tumor necrosis factor-α, interleukin (IL)-1, IL-6) is achieved, thus triggering the expression of enzymes (inducible nitric oxide synthase, manganese superoxide dismutase), anti-apoptotic proteins (Bcl-2), acute phase proteins (haptoglobin, β-fibrinogen), and hepatocyte proliferation. The above responses (i) represent adaptive mechanisms to re-establish redox homeostasis and promote cell survival; (ii) occur via nuclear factor-κB, signal transducer and