Kupffer cell stimulation in the isolated perfused rat liver triggers nuclear factor-κB DNA binding activity

Abstract

Activation of transcription factor NF-kappaB (electrophoretic mobility shift assay) was investigated in the isolated perfused rat liver infused with 0.5 mg of colloidal carbon/ml for 5-20 min, in relation to carbon phagocytosis and carbon-induced O(2) consumption. Experiments were carried out in control rats and in animals treated with the Kupffer cell inactivator gadolinium chloride (GdCl(3)). Carbon uptake and carbon-induced O(2) consumption by perfused livers exhibited a linear increase as a function of the perfusion time, leading to constant O(2)/carbon uptake ratios, with low (0.04-0.15%) fractional sinusoidal lactate dehydrogenase release in the 5-20 min perfusion time studied. NF-kappaB DNA binding activity showed a maximal enhancement at 10 min of carbon perfusion, a response that was sustained at a lower extent at 15 and 20 min of carbon stimulation. After 10 min of carbon infusion, NF-kappaB activation, carbon-induced O(2) consumption, and carbon uptake were diminished by 84%, 94%, and 64% by GdCl(3) treatment (P < 0.05), respectively. It is concluded that the respiratory burst of carbon-stimulated Kupffer cells triggers NF-kappaB activation in the isolated perfused liver, a response that is elicited under optimal conditions of Kupffer cell function and organ viability.

Kupffer Cell-Dependent Signaling in Thyroid Hormone Calorigenesis: Possible Applications for Liver Preconditioning

“…NF-B and STAT3 activation by T 3 administration is suppressed both by the in vivo pretreatments with -tocopherol or N-acetylcysteine (NAC) and with GdCl 3 , prior to hormone treatment. These findings support the contention that T 3 accomplishes the redox activation of hepatic NF-B and STAT3 by actions primarily exerted at the KC level [63,64], and are in agreement with the significant NF-B activation triggered by the respiratory burst of carbon-stimulated KCs found in the isolated perfused rat liver [65].…”

The Relationship Between Thyroid States, Oxidative Stress and Cellular Damage

“…These findings are in agreement with studies showing that the NFB activation can be achieved by physiological levels of the ROS, which are produced during the respiratory burst after stimulation of isolated or cultured macrophages (Kaul & Forman, 1996) and in carbon-stimulated Kupffer cells in the isolated, perfused rat liver (Romanque et al, 2003). This may be caused by the damage produced by the oxidative stress generated by an excess of thyroid hormones.…”

Oxidative Stress and Diseases

“…Fernandez et al found that thyroid calorigenesis is a hormonal stimulus for the REDOX activation of NFB, a response that is triggered in Kupffer cells having higher respiratoryburst activities (Fernandez et al, 2006). These findings are in agreement with studies showing that the NFB activation can be achieved by physiological levels of the ROS, which are produced during the respiratory burst after stimulation of isolated or cultured macrophages (Kaul & Forman, 1996) and in carbon-stimulated Kupffer cells in the isolated, perfused rat liver (Romanque et al, 2003). This may be caused by the damage produced by the oxidative stress generated by an excess of thyroid hormones.…”