Dependence of adaptative regulation for IL-1β action on system A activity in human synovial cells

Human synovial cells are a suitable model for estimating the physiopathological effects of IL‐1β (IL‐1) in joint. Given the importance of this cytokine in the modulation of cell metabolic activities, we set out to study the action of IL‐1 on the neutral amino acid transport A system, using the methyl (aminoisobutyric) acid (MeAIB), the most highly specific and nonmetabolizable substrate for the A system. Stimulation of system A activity by adaptative regulation is a prerequisite to obtain an increase of MeAIB uptake in IL‐1‐treated cells, since cells which had been grown in a normal medium did not express stimulation of system A activity when IL‐1 was added. The IL‐1‐mediated MeAIB uptake is independent of protein synthesis, since cycloheximide (CHX) did not inhibit MeAIB uptake, and characterized by a decrease in the Michaelis constant (Km) (0.147 vs. 0.270 mmol/l, IL‐1 vs. control) and a slight increase in maximal velocity (Vmax) (4.59 vs. 3.89 nmol/mg prot/10 min, IL‐1 vs. control). These observations indicate that IL‐1 induces modifications in both system A transporter affinity and number. Moreover, we indicate that system A should be responsive in vivo to IL‐1 in the same way since derepression and IL‐1 action occurred in the presence of human synovial fluid. © 1996 Wiley‐Liss, Inc.